Induction of NAFLD with Increased Risk of Obesity and Chronic Diseases in Developed Countries


The susceptibility of individuals to obesity has been reported in many developed countries with predisposition of humans to obesity associated with high calorie diets and unhealthy lifestyles. Obesity may closely be involved in cell suicide in various organ diseases with the importance of accelerated aging that requires early intervention with drug therapy to prevent diseases such as non alcoholic fatty liver disease (NAFLD) that has increased in children and reached to approx. 40% of the global population. Obesity is induced by various diets and lifestyle factors such as stress, anxiety and depression which are important to consider with the global increase in obesity and are possibly linked to the rise in individuals with brain disorders that involve neurodegeneration. Xenobiotics such as the endocrine disruptor chemicals that have increased in the environment in various developed countries lead to various chronic endocrine diseases as populations divert towards unhealthy diets and lifestyles with induction of NAFLD and obesity. The amount and nature of food intake that improves and increases liver lipid and xenobiotic metabolism in obese individuals have become important to decrease the risk for increased adiposity in man. High fibre or protein diets that contain leucine may improve liver glucose, lipid and xenobiotic metabolism and require further investigation with xenobiotics such as endocrine disruptors involved in appetite dysregulation and metabolic disorders in developed countries. The use of anti-obese drugs that reduce food intake and improve hypercholesterolemia and cardiovascular disease has been assessed in obesity with drug therapy closely involved either in the prevention or induction of NAFLD and obesity in man.

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Martins, I. (2014) Induction of NAFLD with Increased Risk of Obesity and Chronic Diseases in Developed Countries. Open Journal of Endocrine and Metabolic Diseases, 4, 90-110. doi: 10.4236/ojemd.2014.44011.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] James, P.T., Rigby, N. and Leach, R. (2004) The Obesity Epidemic, Metabolic Syndrome and Future Prevention Strategies. European Journal of Preventive Cardiology, 11, 3-8.
[2] Caballero, B. (2007) The Global Epidemic of Obesity: An Overview. Epidemiologic Reviews, 29, 1-5.
[3] Katzmarzyk, P.T., Church, T.S., Janssen, I., Ross, R. and Blair, S.N. (2005) Metabolic Syndrome, Obesity, and Mortality: Impact of Cardiorespiratory Fitness. Diabetes Care, 28, 391-397.
[4] Rennie, K.L. and Jebb, S.A. (2005) Prevalence of Obesity in Great Britain. Obesity Reveiws, 6, 11-12.
[5] de la Monte, S.M., Longato, L., Tong, M. and Wands, J.R. (2009) Insulin Resistance and Neurodegeneration: Roles of Obesity, Type 2 Diabetes Mellitus and Non-Alcoholic Steatohepatitis. Current Opinion in Investigational Drugs, 10, 1049-1060.
[6] Fabbrini, E., Sullivan, S. and Klein, S. (2010) Obesity and Nonalcoholic Fatty Liver Disease: Biochemical, Metabolic, and Clinical Implications. Hepatology, 51, 679-689.
[7] Bleich, S.N., Cutler, D., Murray, C. and Adams, A. (2008) Why Is the Developed World Obese? Annual Review of Public Health, 29, 273-295.
[8] Lavie, C.J., Mehra, M.R. and Milani, R.V. (2005) Obesity and Heart Failure Prognosis: Paradox or Reverse Epidemiology? European Heart Journal, 26, 5-7.
[9] Mathew, B., Francis, L., Kayalar, A. and Cone, J. (2008) Obesity: Effects on Cardiovascular Disease and Its Diagnosis. Journal of the American Board of Family Medicine, 21, 562-568.
[10] Martins, I.J., Creegan, R., Lim, W.L.F. and Martins, R.N. (2013) Molecular Insights into Appetite Control and Neuroendocrine Disease as Risk Factors for Chronic Diseases in Western Countries. Special Issue. Molecular Mechanisms Involved in Inflammation and Insulin Resistance in Chronic Diseases and Possible Interventions. Open Journal of Endocrine and Metabolic Diseases, 3, 11-33.
[11] Brody, J. (2002) The Global Epidemic of Childhood Obesity: Poverty, Urbanization, and the Nutrition Transition. Nutrition Bytes, 8, 1-7.
[12] Roberts, E.A. (2005) Non-Alcoholic Fatty Liver Disease (NAFLD) in Children. Frontiers in Bioscience, 10, 2306-2318.
[13] Vos, M.B. and McClain, C.J. (2008) Nutrition and Nonalcoholic Fatty Liver Disease in Children. Current Diabetes Reports, 8, 399-406.
[14] Martins, I.J. (2013) Increased Risk for Obesity and Diabetes with Neurodegeneration in Developing Countries. Journal of Molecular and Genetic Medicine, S1, 001.
[15] Pearce, E.N. (2012) Thyroid Hormone and Obesity. Current Opinion in Endocrinology, Diabetes & Obesity, 19, 408-413.
[16] Reinehr, T. (2010) Obesity and Thyroid Function. Molecular and Cellular Endocrinology, 316, 165-171.
[17] Biondi, B. (2010) Thyroid and Obesity: An Intriguing Relationship. Journal of Clinical Endocrinology & Metabolism, 95, 3614-3617.
[18] Poulain, M., Doucet, M., Major, G.C., Drapeau, V., Sériès, F., Boulet, L.P., Tremblay, A. and Maltais, F. (2006) The Effect of Obesity on Chronic Respiratory Diseases: Pathophysiology and Therapeutic Strategies. Canadian Medical Association Journal, 174, 1293-1299.
[19] Salome, C.N., King, G.G. and Berend, N. (2010) Physiology of Obesity and Effects on Lung Function. Journal of Applied Physiology, 108, 206-211.
[20] Mietwally, M., Ledger, W.L. and Li, T.C. (2008) Reproductive Endocrinology and Clinical Aspects of Obesity in Women. Annals of the New York Academy of Sciences, 1127, 140-146.
[21] Martínez, J., et al. (2004) Is Obesity a Risk Factor in Acute Pancreatitis? A Meta-Analysis. Pancreatology, 4, 42-48.
[22] Veeraish, C., Vaid, M., Chauhan, N. and Parashar, A. (2012) The Obesity Epidemic and Kidney Disease: A Literature Review. In: Sahay, M., Ed., Diseases of Renal Parenchyma, Chapter 4, 1-56.
[23] Abrass, C.K. (2004) Overview: Obesity: What Does It Have to Do with Kidney Disease? Journal of the American Society of Nephrology, 15, 2768-2772.
[24] Wells, J.C., Marphatia, A.A., Cole, T.J. and McCoy, D. (2012) Associations of Economic and Gender Inequality with Global Obesity Prevalence: Understanding the Female Excess. Social Science & Medicine, 75, 482-490.
[25] Winter, Y., Rohrmann, S., Linseisen, J., Lanczik, O., Ringleb, P.A., Hebebrand, J. and Back, T. (2008) Contribution of Obesity and Abdominal Fat Mass to Risk of Stroke and Transient Ischemic Attacks. Stroke, 39, 3145-3151.
[26] Pannacciulli, N., Del Parigi, A., Chen, K.W., Le, D.S.N.T., Reiman, E.M. and Tataranni, P.A. (2006) Brain Abnormalities in Human Obesity: A Voxel-Based Morphometric Study. NeuroImage, 31, 1419-1425.
[27] Raji, C.A., Ho, A.J., Parikshak, N.N., Becker, J.T., Lopez, O.L., Kuller, L.H., Hua, X., Leow, A.D., Toga, A.W. and Thompson, P.M. (2010) Brain Structure and Obesity. Human Brain Mapping, 31, 353-364.
[28] Yau, P.L., Castro, M.G., Tagani, A., Tsui, W.H. and Convit, A. (2012) Obesity and Metabolic Syndrome and Functional and Structural Brain Impairments in Adolescence. Pediatrics, 130, e856-864.
[29] Whitmer, R.A., Gunderson, E.P., Barrett-Connor, E., Quesenberry Jr., C.P. and Yaffe, K. (2005) Obesity in Middle Age and Future Risk of Dementia: A 27 Year Longitudinal Population Based Study. British Medical Journal, 330, 1360.
[30] Froy, O. (2010) Metabolism and Circadian Rhythms—Implications for Obesity. Endocrine Reviews, 31, 1-24.
[31] Mendoza, J. and Challet, E. (2009) Brain Clocks: From the Suprachiasmatic Nuclei to a Cerebral Network. The Neuroscientist, 15, 477-488.
[32] Saper, C.B., Lu, J., Chou, T.C. and Gooley, J. (2005) The Hypothalamic Integrator for Circadian Rhythms. Trends in Neurosciences, 28, 152-157.
[33] Yildiz, B.O., Suchard, M.A., Wong, M.L., McCann, S.M. and Licinio, J. (2004) Alteration in the Dynamics of Circulating Ghrelin, Adiponectin and Leptin in Human Obesity. Proceedings of the National Academy of Sciences of the United States of America, 101, 10434-10439.
[34] Kalra, S.P., Bagnasco, M., Otukonyong, E.E., Dube, M.G. and Kalra, P.S. (2003) Rhythmic, Reciprocal Ghrelin and Leptin Signaling: New Insight in the Development of Obesity. Regulatory Peptides, 111, 1-11.
[35] Kalsbeek, A., Fliers, E., Romijn, J.A., la Fleur, S.E., Wortel, J., Bakker, O., Endert, E. and Buijs, R.M. (2001) The Suprachiasmatic Nucleus Generates the Diurnal Changes in Plasma Leptin Levels. Endocrinology, 142, 2677-2685.
[36] Horvath, T.L., Castaneda, T., Tang-Christensen, M., Pagotto, U. and Tschop, M.H. (2003) Ghrelin as a Potential Anti-Obesity Target. Current Pharmaceutical Design, 9, 1383-1395.
[37] Escobar, C., et al. (2009) Peripheral Oscillators: the Driving Force for Food-Anticipatory Activity. European Journal of Neuroscience, 30, 1665-1675.
[38] Russcher, M., Koch, B., Nagtegaal, E., van der Putten, K., ter Wee, P. and Gaillard, C. (2012) The Role of Melatonin Treatment in Chronic Kidney Disease. Frontiers in Bioscience (Landmark Edition), 17, 2644-2656.
[39] Wu, L. and Reddy, A.B. (2013) Disrupting Rhythms: Diet-Induced Obesity Impairs Diurnal Rhythms in Metabolic Tissues. Diabetes, 62, 1829-1830.
[40] Bray, M.S. and Young, M.E. (2007) Circadian Rhythms in the Development of Obesity: Potential Role for the Circadian Clock within the Adipocyte. Obesity Reviews, 8, 169-181.
[41] Monti, J.M., Torterolo, P. and Lagos, P. (2013) Melanin-Concentrating Hormone Control of Sleep-Wake Behaviour. Sleep Medicine Reviews, 17, 293-298.
[42] Lerchl, A. and Reiter, R.J. (2012) Treatment of Sleep Disorders with Melatonin. British Medical Journal, 345, e6968.
[43] Gillette, M.U. and McArthur, A.J. (1996) Circadian Actions of Melatonin at the Suprachiasmatic Nucleus. Behavioural Brain Research, 73, 135-139.
[44] Cizza, G., Skarulis, M. and Mignot, E. (2005) A Link Between Short Sleep and Obesity: Building the Evidence for Causation. Sleep, 28, 1217-1220.
[45] Gangswisch, J.E., Malaspina, D., Boden-Albala, B. and Heymsfield, S.B. (2005) Inadequate Sleep as a Risk Factor for Obesity: Analysis of the NHANES I. Sleep, 28, 1289-1296.
[46] Gimble, J.M., Bray, M.S. and Young, A. (2009) Circadian Biology and Sleep: Missing Links in Obesity and Metabolism? Obesity Reviews, 10, 1-5.
[47] Reiter, R.J., Tan, D.X., Korkmaz, A. and Ma, S. (2011) Obesity and Metabolic Syndrome: Association with Chronodisruption, Sleep Deprivation, and Melatonin Suppression. Annals of Medicine, 44, 564-577.
[48] Taheri, S., Lin, L., Austin, D., Young, T. and Mignot, E. (2004) Short Sleep Duration Is Associated with Reduced Leptin, Elevated Ghrelin, and Increased Body Mass Index. PLoS Medicine, 1, e62.
[49] Lyon, H.N. and Hirschhorn, J.N. (2005) Genetics of Common Forms of Obesity: A Brief Overview. American Journal of Clinical Nutrition, 82, 215S-217S.
[50] Walley, A.J., Blakemore, A.I.F. and Froguel, P. (2006) Genetics of Obesity and the Prediction of Risk for Health. Human Molecular Genetics, 15, R124-R130.
[51] Mutch, D.M. and Clément, K. (2006) Unraveling the Genetics of Human Obesity. PLoS Genetics, 2, e188.
[52] Choi, S.W. and Friso, S. (2010) Epigenetics: A New Bridge between Nutrition and Health. Advances in Nutrition, 1, 8-16.
[53] Samaras, T. and Elrick, H. (2005) An Alternative Hypothesis to the Obesity Epidemic: Obesity Is Due to Increased Maternal Body Size, Birth Size, Growth Rate, and Height. Medical Hypotheses, 65, 676-682.
[54] Guarente, L. (2007) Sirtuins in Aging and Disease. Cold Spring Harbour Symposium Quantitative Biology, 72, 483-488.
[55] Hansen, M.K. and Connolly, T.M. (2008) Nuclear Receptors as Drug Targets in Obesity, Dyslipidemia and Atherosclerosis. Current Opinion in Investigational Drugs, 9, 247-255.
[56] Harrison, C. (2012) Neurodegenerative Disorders: A Neuroprotective Role for Sirtuin 1. Nature Reviews Drug Discovery, 11, 108.
[57] Kawada, T., Goto, T., Hirai, S., Kang, M.S., Uemura, T., Yu, R. and Takahashi, N. (2008) Dietary Regulation of Nuclear Receptors in Obesity-Related Metabolic Syndrome. Asia Pacific Journal of Clinical Nutrition, 17, 126-130.
[58] Swanson, H.I., Wada, T., Xie, W., Renga, B., Zampella, A., Distrutti, E., Fiorucci, S., Kong, B., Thomas, A.M., Guo, G.L., Narayanan, R., Yepuru, M., Dalton, J.T. and Chiang, J.Y.L. (2013) Role of Nuclear Receptors in Lipid Dysfunction and Obesity-Related Diseases. Drug Metabolism & Disposition, 41, 1-11.
[59] Cakir, I., Perello, M., Lansari, O., Messier, N.J., Vaslet, C.A. and Nillni, E.A. (2009) Hypothalamic Sirt1 Regulates Food Intake in a Rodent Model System. PLoS ONE, 4, e8322.
[60] Kitamura, T. and Sasaki, T. (2012) Hypothalamic Sirt1 and Regulation of Food Intake. Diabetology International, 3, 109-112.
[61] Dietrich, M.O., Antunes, C., Geliang, G., Liu, Z.W., Borok, E., Nie, Y.Z., Xu, A.W., Souza, D.O., Gao, Q., Diano, S., Gao, X.B. and Horvath, T.L. (2010) Agrp Neurons Mediate Sirt1’s Action on the Melanocortin System and Energy Balance: Roles for Sirt1 in Neuronal Firing and Synaptic Plasticity. Journal of Neuroscience, 30, 11815-11825.
[62] Schaffhauser, A.O., Madiehe, A.M., Braymer, H.D., Bray, G.A. and York, D.A. (2002) Effects of a High-Fat Diet and Strain on Hypothalamic Gene Expression in Rats. Obesity Research, 10, 1188-1196.
[63] Lee, A.K., Mojtahed-Jaberi, M., Kyriakou, T., Astarloa, E.A.O., Arno, M., Marshall, N.J., Brain, S.D. and O’Dell, S.D. (2010) Effect of High-Fat Feeding on Expression of Genes Controlling Availability of Dopamine in Mouse Hypothalamus. Nutrition, 26, 411-422.
[64] Garaulet, M., Esteban Tardido, A., Lee, Y.C., Smith, C.E., Parnell, L.D. and Ordovás, J.M. (2012) SIRT1 and CLOCK 3111T>C Combined Genotype Is Associated with Evening Preference and Weight Loss Resistance in a Behavioral Therapy Treatment for Obesity. International Journal of Obesity, 36, 1436-1441.
[65] Shimoyama, Y., Suzuki, K., Hamajima, N. and Niwa, T. (2011) Sirtuin 1 Gene Polymorphisms Are Associated with Body Fat and Blood Pressure in Japanese. Translational Research, 157, 339-347.
[66] Shimoyama, Y., Mitsuda, Y., Tsuruta, Y., Suzuki, K., Hamajima, N. and Niwa, T. (2012) SIRTUIN 1 Gene Polymorphisms Are Associated with Cholesterol Metabolism and Coronary Artery Calcification in Japanese Hemodialysis Patients. Journal of Renal Nutrition, 22, 114-119.
[67] Clark, S.J., Falchi, M., Olsson, B., et al. (2012) Association of Sirtuin 1 (SIRT1) Gene SNPs and Transcript Expression Levels with Severe Obesity. Obesity (Silver Spring), 20, 178-185.
[68] Flachsbart, F., Croucher, P.J.P., Nikolaus, S., Hampe, J., Cordes, C., Schreiber, S. and Nebela, A. (2006) Sirtuin 1 (SIRT1) Sequence Variation Is Not Associated with Exceptional Human Longevity. Experimental Gerontology, 41, 98-102.
[69] Cohen, D.E., Supinski, A.M., Bonkowski, M.S., Donmez, G. and Guarente, L.P. (2009) Neuronal SIRT1 Regulates Endocrine and Behavioral Responses to Calorie Restriction. Genes & Development, 23, 2812-2817.
[70] Moore, R.L. and Faller, D.V. (2013) SIRT1 Represses Estrogen-Signaling, Ligand-Independent ERα-Mediated Transcription, and Cell Proliferation in Estrogen-Responsive Breast Cells. Journal of Endocrinology, 216, 273-285.
[71] Liang F, Kume S, Koya D, Kume, S. and Daisuke, K. (2009) SIRT1 and Insulin Resistance. Nature Reviews. Endocrinology, 5, 367-373.
[72] Takano, A., Haruta, T., Iwata, M., Usui, I., Uno, T., Kawahara, J., Ueno, E., Sasaoka, T. and Kobayashi, M. (2001) Growth Hormone Induces Cellular Insulin Resistance by Uncoupling Phosphatidylinositol 3-Kinase and Its Downstream Signals in 3T3-L1 Adipocytes. Diabetes, 50, 1891-1900.
[73] Kitada, M., Kume, S., Takeda-Watanabe, A., Kanasaki, K. and Koya, D. (2013) Sirtuins and Renal Diseases: Relationship with Aging and Diabetic Nephropathy. Clinical Science, 124, 153-164.
[74] Rajendrasozhan, S., Yang, S.R., Kinnula, V.L. and Rahman, I. (2008) SIRT1, an Antiinflammatory and Antiaging Protein, Is Decreased in Lungs of Patients with Chronic Obstructive Pulmonary Disease. American Journal Respiration Critical Care Medicine, 177, 861-870.
[75] Archer, R. and Baker, E.H. (2009) Diabetes and Metabolic Dysfunction in COPD. Respiratory Medicine, 5, 67-74.
[76] Kang, J.E., Lim, M.M., Bateman, R.J., Lee, J.J., Smyth, L.P., Cirrito, J.R., Fujiki, N., Nishino, S. and Holtzman, D.M. (2009) Amyloid-Beta Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle. Science, 326, 1005-1007.
[77] Xie, H., Sun, L. and Lodish, H.F. (2009) Targeting MicroRNAs in Obesity. Expert Opinion on Therapeutic Targets, 13, 1227-1238.
[78] Huangming, X., Lim, B. and Lodish, H.F. (2009) MicroRNAs Induced during Adipogenesis that Accelerate Fat Cell Development Are Downregulated in Obesity. Diabetes, 58, 1050-1057.
[79] McGregor, R.A. and Choi, M.S. (2011) microRNAs in the Regulation of Adipogenesis and Obesity. Current Molecular Medicine, 11, 304-316.
[80] Lee, J. and Kemper, J.K. (2010) Controlling SIRT1 Expression by microRNAs in Health and Metabolic Disease. Aging (Albany NY), 2, 527-534.
[81] Tsai, K.L., Chen, L.H., Chen, Y.C., Kao, C.L., Chen, L.K. and Chiou, S.H. (2011) The Role of microRNAs in Modulating Sirtuin 1 Expression. Journal of Clinical Gerontology and Geriatrics, 2, 71-75.
[82] Christine, P., Cambridge, E.L., Lelliott, C.J., Carragher, D.M., Estabel, J., Gerdin, A.K., Karp, N.A., Scudamore, C.L., Ramirez-Solis, R. and White, J.K. (2013) High-Fat Feeding Rapidly Induces Obesity and Lipid Derangements in C57BL/6N Mice. Mammalian Genome, 24, 240-251.
[83] Hsuchou, H., He, Y., Kastin, A.J., Tu, H., Markadakis, E.N., Rogers, R.C., Fossier, P.B. and Pan, W.H. (2009) Obesity Induces Functional Astrocytic Leptin Receptors in Hypothalamus. Brain, 132, 889-902.
[84] Bunyan, J., Murell, E.A. and Shah, P.P. (1976) The Induction of Obesity in Rodents by Means of Monosodium Glutamate. British Journal of Nutrition, 35, 25-39.
[85] Wang, C.Y. and Liao, J.K. (2012) A Mouse Model of Diet-Induced Obesity and Insulin Resistance. Methods in Molecular Biology, 821, 421-433.
[86] Lin, S., Thomas, T.C., Storlien, L.H. and Huang, X.F. (2000) Development of High Fat Diet-Induced Obesity and Leptin Resistance in C57Bl/6J Mice. International Journal of Obesity, 24, 639-646.
[87] Peng, Y., Rideout, D., Rakita, S., Lee, J. and Murr, M. (2012) Diet-Induced Obesity Associated with Steatosis, Oxidative Stress, and Inflammation in Liver. Surgical for Obesity and Related Diseases, 8, 73-81.
[88] Anstee, Q.M. and Goldin, R.D. (2006) Mouse Models in Non-Alcoholic Fatty Liver Disease and Steatohepatitis Research. International Journal of Experimental Pathology, 87, 1-16.
[89] Browning, J.D. and Horton, J.D. (2004) Molecular Mediators of Hepatic Steatosis and Liver Injury. Journal of Clinical Investigation, 114, 147-152.
[90] Qatanani, M. and Lazar, M.A. (2007) Mechanisms of Obesity-Associated Insulin Resistance: Many Choices on the Menu. Genes & Development, 21, 1443-1455.
[91] Martins, I.J. and Redgrave, T.G. (2004) Obesity and Post-Prandial Lipid Metabolism. Feast or Famine? Journal of Nutritional Biochemistry, 15, 130-141.
[92] Martins, I.J., Tran, J.M. and Redgrave, T.G. (2002) Food Restriction Normalizes Chylomicron Remnant Metabolism in Murine Models of Obesity as Assessed by a Novel Stable Isotope Breath Test. Journal of Nutrition, 132, 176-181.
[93] Martins, I.J., Sainsbury, A.J., Mamo, J.C. and Redgrave, T.G. (1994) Lipid and Apolipoprotein B48 Transport in Mesenteric Lymph and the Effect of Hyperphagia on the Clearance of Chylomicron-Like Emulsions in Insulin-Deficient Rats. Diabetologia, 37, 238-246.
[94] Dane-Stewart, C.A., Watts, G.F., Barrett, P.H.R., Stuckey, B.G.A., Mamo, J.C.L., Martins, I.J. and Redgrave, T.G. (2003) Chylomicron Remnant Metabolism Studied with a New Breath Test in Postmenopausal Women with and without Type 2 Diabetes Mellitus. Clinical Endocrinology, 58, 415-420.
[95] Watts, G.F., Chan, D.C.F., Barrett, P.H.R., Martins, I.J. and Redgrave, T.G. (2001) Preliminary Experience with a New Stable Isotope Breath Test for Chylomicron Remnant Metabolism: A Study in Central Obesity. Clinical Science, 101, 683-690.
[96] Chan, D.C., Watts, G.F., Barrett, P.H., Martins, I.J., James, A.P., Mamo, J.C., Mori, T.A. and Redgrave, T.G. (2002) Effect of Atorvastatin on Chylomicron Remnant Metabolism in Visceral Obesity: A Study Employing a New Stable Isotope Breath Test. Journal of Lipid Research, 43, 706-712.
[97] Martins, I.J., Mortimer, B.C., Miller, J. and Redgrave, T.G. (1996) Effects of Particle Size and Number on the Plasma Clearance of Chylomicrons and Remnants. Journal of Lipid Research, 37, 2696-2705.
[98] Casals-Casas, C. and Desvergne, B. (2011) Endocrine Disruptors: From Endocrine to Metabolic Disruption. Annual Review of Physiology, 73, 135-162.
[99] Grün, F. and Blumberg, B. (2009) Endocrine Disrupters as Obesogens. Molecular and Cellular Endocrinology, 304, 19-29.
[100] Polyzos, S.A., Kountouras, J., Deretzi, G., Zavos, C. and Mantzoros, C.S. (2012) The Emerging Role of Endocrine Disruptors in Pathogenesis of Insulin Resistance: A Concept Implicating Nonalcoholic Fatty Liver Disease. Current Molecular Medicine, 12, 68-82.
[101] Elobeid, M.A. and Alison, D.B. (2008) Putative Environmental-Endocrine Disruptors and Obesity: A Review. Current Opinion in Endocrinology, Diabetes & Obesity, 15, 403-408.
[102] Arciello, M., Gori, M., Maggio, R., Barbaro, B., Tarocchi, M., Galli, A. and Balsano, C. (2013) Environmental Pollution: A Tangible Risk for NAFLD Pathogenesis. International Journal of Molecular Sciences, 14, 22052-22066.
[103] Yu, W., Laseter, J. and Mylander, C. (2011) Persistent Organic Pollutants in Serum and Several Different Fat Compartments in Humans. Journal of Environmental and Public Health, 2011, Article ID: 417980, 8 pages.
[104] Schug, T.T., Janesick, A., Blumberg, B. and Heindel, J.J. (2011) Endocrine Disrupting Chemicals and Disease Susceptibility. Journal Steroid Biochemistry Molecular Biology, 127, 204-215.
[105] Jarrett, R.E. (2000) Endocrine Disruptor Chemicals as a Rising Compliance Issue. Federal Facilities Environmental Journal, 11, 25-39.
[106] Manning, T. (2005) Endocrine-Disrupting Chemicals: A Review of the State of the Science. Australasian Journal of Ecotoxicology, Endocrine Disrupting Chemicals Review, 11, 1-52
[107] Martins, I.J., Lim, W.L.F., Wilson, A.C., Laws, S.M. and Martins, R.N. (2013) The Acceleration of Aging and Alzheimer’s Disease through the Biological Mechanisms behind Obesity and Type II Diabetes. Health, 5, 913-920.
[108] Martins, I.J., Wilson, A.C., Lim, W.L.F., Laws, S.M., Fuller, S.J. and Martins, R.N. (2012) Sirtuin-1 Mediates the Obesity Induced Risk of Common Degenerative Diseases: Alzheimer’s Disease, Coronary Artery Disease and Type 2 Diabetes. Health, 4, 1448-1456.
[109] Salminen, A., Kaarniranta, K. and Kauppinen, A. (2013) Crosstalk between Oxidative Stress and SIRT1: Impact on the Aging Process. International Journal of Molecular Sciences, 14, 3834-3859.
[110] Caito, S., Rajendrasozhan, S., Cook, S., Chung, S., Yao, H.W., Friedman, A.E., Brookes, P.S. and Rahman, I. (2010) SIRT1 Is a Redox-Sensitive Deacetylase that Is Post-Translationally Modified by Oxidants and Carbonyl Stress. FASEB Journal, 24, 3145-3159.
[111] Xu, F., Gao, Z.G., Zhang, J., Rivera, C.A., Yin, J., Weng, J.P. and Ye, J.P. (2010) Lack of SIRT1 (Mammalian Sirtuin 1) Activity Leads to Liver Steatosis in the SIRT1+/-Mice: A Role of Lipid Mobilization and Inflammation. Endocrinology, 151, 2504-2514.
[112] Purushotham, A., Xu, Q. and Li, X.L. (2012) Systemic SIRT1 Insufficiency Results in Disruption of Energy Homeostasis and Steroid Hormone Metabolism upon High-Fat-Diet Feeding. FASEB Journal, 26, 656-667.
[113] Bordone, L., Cohen, D., Robinson, A., Motta, M.C., Van Veen, E., Czopik, A., Steele, A.D., Crowe, H., Marmor, S., Luo, J.Y., Gu, W. and Guarente, L. (2007) SIRT1 Transgenic Mice Show Phenotypes Resembling Calorie Restriction. Aging Cell, 6, 759-767.
[114] Hao, C., Cheng, X.J., Xia, H.F. and Ma, X. (2012) The Endocrine Disruptor Mono-(2-ethylhexyl) Phthalate Promotes Adipocyte Differentiation and Induces Obesity in Mice. Bioscience Reports, 32, 619-629.
[115] Bility, M.T., Thompson, J.T., McKee, R.H., David, R.M., Butala, J.H., Vanden Heuvel, J.P. and Peters, J.M. (2004) Activation of Mouse and Human Peroxisome Proliferator-Activated Receptors (PPARs) by Phthalate Monoesters. Toxicological Sciences, 82, 170-182.
[116] De Coster, S. and van Larebeke, N. (2012) Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action. Journal of Environmental and Public Health, 2012, Article ID: 713696, 52 pages.
[117] Sun, Y., Guo, Z.K., Iku, S., Saito, T. and Kurasaki, M. (2013) Diethyl Phthalate Enhances Expression of SIRT1 and DNMT3a during Apoptosis in PC12 Cells. Journal of Applied Toxicology, 33, 1484-1492.
[118] Kambia, N., Renault, N., Dilly, S., Farce, A., Dine, T., Gressier, B., Luyckx, M., Brunet, C. and Chavatte, P. (2008) Molecular Modelling of Phthalates-PPARs Interactions. Journal of Enzyme Inhibition and Medicinal Chemistry, 23, 611-616.
[119] Martina, C.A., Weiss, B. and Swan, S.H. (2012) Lifestyle Behaviours Associated with Exposures to Endocrine Disruptors. NeuroToxicology, 33, 1427-1433.
[120] Wang, J., Lv, X.W., Shi, J.P. and Hu, X.S. (2006) Ceramide Induces Apoptosis via a Peroxisome Proliferator-Activated Receptor Gamma-Dependent Pathway. Apoptosis, 11, 2043-2052.
[121] LeCluyse, E.L. (2001) Pregnane X Receptor: Molecular Basis for Species Differences in CYP3A Induction by Xenobiotics. Chemico-Biological Interactions, 134, 283-289.
[122] Gao, J. and Xie, W. (2010) Pregnane X Receptor and Constitutive Androstane Receptor at the Crossroads of Drug Metabolism and Energy Metabolism. Drug Metabolism & Disposition, 38, 2091-2095.
[123] Spruiell, K., Richardson, R.M., Cullen, J.M., Awumey, E.M., Gonzalez, F.J. and Gyamfi, M.A. (2014) Role of Pregnane X Receptor in Obesity and Glucose Homeostasis in Male Mice. Journal of Biological Chemistry, 289, 3244-3261.
[124] Shelness, G.S. and Rudel, L.L. (2005) A Role for the Pregnane X Receptor in High-Density Lipoprotein Metabolism. Arteriosclerosis, Thrombosis, and Vascular Biology, 25, 2016-2017.
[125] Masson, D., Lagrost, L., Athias, A., Gambert, P., Brimer-Cline, C., Lan, L., Schuetz, J.D., Schuetz, E.G. and Assem, M. (2005) Expression of the Pregnane X Receptor in Mice Antagonizes the Cholic Acid-Mediated Changes in Plasma Lipoprotein Profile. Arteriosclerosis, Thrombosis, and Vascular Biology, 25, 2164-2169.
[126] Hukkanen, J., Hakkola, J. and Rysa, J. (2012) Pregnane X Receptor (PXR)—A Contributor to the Diabetes Epidemic? Drug Metabolism and Drug Interactions, 29, 3-15.
[127] Neel, B.A. and Sargis, R.M. (2011) The Paradox of Progress: Environmental Disruption of Metabolism and the Diabetes Epidemic. Diabetes, 60, 1838-1848.
[128] Wingfield, J.C. and Mukai, M. (2009) Endocrine Disruption in the Context of Life Cycles: Perception and Transduction of Environmental Cues. General and Comparative Endocrinology, 163, 92-96.
[129] Zmrzljak, U.P. and Rozman, D. (2012) Circadian Regulation of the Hepatic Endobiotic and Xenobitoic Detoxification Pathways: The Time Matters. Chemical Research in Toxicology, 25, 811-824.
[130] Claudel, T., Cretenet, G., Saumet, A. and Gachon, F. (2007) Crosstalk between Xenobiotics Metabolism and Circadian Clock. FEBS Letters, 581, 3626-3633.
[131] Wang, X.H., Fang, X., Zhou, J., Chen, Z., Zhao, B.L., Xiao, L., Liu, A., Li, Y.S.J., Shyy, J.Y.J., Guan, Y.F., Chien, S. and Wang, N.P. (2013) Shear Stress Activation of Nuclear Receptor PXR in Endothelial Detoxification. Proceedings of the National Academy of Sciences of the United States of America, 110, 13174-13179.
[132] Wu-Wong, J.R. (2008) Endothelial Dysfunction and Chronic Kidney Disease: Treatment Options. Current Opinion in Investigational Drugs, 9, 970-982.
[133] Herrera, M.D., Mingorance, C., Rodríguez-Rodríguez, R. and de Sotomayor, M.A. (2010) Endothelial Dysfunction and Aging: An Update. Ageing Research Reviews, 9, 142-152.
[134] Arao, T., Takabatake, N., Sata, M., Abe, S., Shibata, Y., Honma, T., Takahashi, K., Okada, A., Takeishi, Y. and Kubota, I. (2003) In Vivo Evidence of Endothelial Injury in Chronic Obstructive Pulmonary Disease by Lung Scintigraphic Assessment of (123)I-Metaiodobenzylguanidine. Journal of Nuclear Medicine, 44, 1747-1754.
[135] Perticone, F., Ceravolo, R., Candigliota, M., Ventura, G., Iacopino, S., Sinopoli, F. and Mattioli, P.L. (2001) Obesity and Body Fat Distribution Induce Endothelial Dysfunction by Oxidative Stress: Protective Effect of Vitamin C. Diabetes, 50, 159-165.
[136] Steinberg, H.O., Chaker, H., Leaming, R., Johnson, A., Brechtel, G. and Baron, A.D. (1996) Obesity/Insulin Resistance Is Associated with Endothelial Dysfunction. Implications for the Syndrome of Insulin Resistance. Journal of Clinical Investigation, 97, 2601-2610.
[137] Schinkel, A.H. (1999) P-Glycoprotein, a Gatekeeper in the Blood-Brain Barrier. Advanced Drug Delivery Reviews, 36, 179-194.
[138] Garrigues, A., Escargueil, A.E. and Orlowski, S. (2002) The Multidrug Transporter, P-Glycoprotein, Actively Mediates Cholesterol Redistribution in the Cell Membrane. Proceedings of the National Academy of Sciences of the United States of America, 99, 10347-10352.
[139] Le Goff, W., Settle, M., Greene, D.J., Morton, R.E. and Smith, J.D. (2006) Reevaluation of the Role of the Multidrug-Resistant P-Glycoprotein in Cellular Cholesterol Homeostasis. Journal of Lipid Research, 47, 51-58.
[140] Wessler, J.D., Grip, L.T., Mendell, J. and Giugliano, R.P. (2013) The P-Glycoprotein Transport System and Cardiovascular Drugs. Journal of American College of Cardiology, 61, 2495-2502.
[141] Wittgen, H.G., Greupink, R., van den Heuvel, J.J., van den Broek, P.H., Dinter-Heidorn, H., Koenderink, J.B. and Russel, F.G. (2012) Exploiting Transport Activity of p-Glycoprotein at the Blood-Brain Barrier for the Development of Peripheral Cannabinoid Type 1 Receptor Antagonists. Molecular Pharmaceutics, 9, 1351-1360.
[142] Foucaud-Vignault, M., Soayfane, Z., Ménez, C., Bertrand-Michel, J., Martin, P.G.P., Guillou, H., Collet, X. and Lespine, A. (2011) P-Glycoprotein Dysfunction Contributes to Hepatic Steatosis and Obesity in Mice. PLoS ONE, 6, e23614.
[143] Abuznait, A.H., Cain, C., Ingram, D., Burk, D. and Kaddoum, A. (2011) Up-Regulation of P-Glycoprotein Reduces Intracellular Accumulation of Beta Amyloid: Investigation of P-Glycoprotein as a Novel Therapeutic Target for Alzheimer’s Disease. Journal of Pharmacy and Pharmacology, 63, 1111-1118.
[144] Lam, F.C., Liu, R.H., Lu, P.H., Shapiro, A.B., Renoir, J.M., Sharom, F.J. and Reiner, P.B. (2001) Beta-Amyloid Efflux Mediated by p-Glycoprotein. Journal of Neurochemistry, 76, 1121-1128.
[145] Rigalli, P., Ruiz, M.L., Perdomo, V.G., Villanueva, S.S.M., Mottino, A.D. and Catania, V.A. (2011) Pregnane X Receptor Mediates the Induction of P-Glycoprotein by Spironolactone in HepG2 Cells. Toxicology, 285, 18-24.
[146] Bauer, B., Hartz, A.M., Fricker, G. and Miller, D.S. (2004) Pregnane X Receptor Up-Regulation of P-Glycoprotein Expression and Transport Function at the Blood-Brain Barrier. Molecular Pharmacology, 66, 413-419.
[147] Cheng, X. and Klaassen, C.D. (2009) Tissue Distribution, Ontogeny, and Hormonal Regulation of Xenobiotic Transporters in Mouse Kidneys. Drug Metabolism & Disposition, 37, 2178-2185.
[148] Lock, E.A. and Reed. C.J. (1998) Xenobiotic Metabolizing Enzymes of the Kidney. Toxicologic Pathology, 26, 18-25.
[149] Dember, L.N. (2006) Amyloidosis-Associated Kidney Disease. Journal of the American Society of Nephrology, 17, 3458-3471.
[150] Wang, Y., Chen, X.L., Klag, M.J. and Caballero, B. (2006) Epidemic of Childhood Obesity: Implications for Kidney Disease. Advances in Chronic Kidney Disease, 13, 336-351.
[151] Rodgers, J.R., Tschop, M.H. and Wilding, J.P.H. (2012) Anti-Obesity Drugs: Past, Present and Future. Disease Models & Mechanisms, 5, 621-626.
[152] Hainer, V. and Hainerová, I.A. (2012) Do We Need Anti-Obesity Drugs? Diabetes/Metabolism Research and Reveiws, 28, 8-20.
[153] Gosden, D.J. and Smith, S.L. (2012) What Is the Prognosis for New Centrally-Acting Anti-Obesity Drugs? Neuropharmacology, 63, 132-146.
[154] Hatahet, M.A. and Dhurandhar, N.V. (2002) Antiobesity Drugs: Current and Future Issues. Current Diabetes Reports, 2, 409-415.
[155] Halford, J.C.G. and Blundell, J.E. (2000) Pharmacology of Appetite Suppression. Progress in Drug Research, 54, 25-58.
[156] Adan, R.A.H. (2013) Mechanisms Underlying Current and Future Anti-Obesity Drugs. Trends in Neurosciences, 36, 133-140.
[157] Derosa, G. and Maffioli, P. (2012) Anti-Obesity Drugs: A Review about Their Effects and Their Safety. Expert Opinion on Drug Safety, 11, 459-471.
[158] Elangbam, C.S. (2009) Current Strategies in the Development of Anti-Obesity Drugs and Their Safety Concerns. Veterinary Pathology, 46, 10-24.
[159] Li, M.F. and Cheung, B.M.Y. (2011) Rise and Fall of Anti-Obesity Drugs. World Journal of Diabetes, 2, 19-23.
[160] Hooft, R. (2003) Drug Discovery and Development for Metabolic Diseases. Drug Discovery Today, 8, 1064-1066.
[161] Finer, N. (2002) Pharmacotherapy of Obesity. Best Practice & Research Clinical Endocrinology & Metabolism, 16, 717-742.
[162] Loannides-Demos, L.L., Piccenna, L. and John, J. (2011) Pharmacotherapies for Obesity: Past, Current, and Future Therapies. Journal of Obesity, 2011, Article ID: 179674.
[163] Fong, T.M. (2008) Development of Anti-Obesity Agents: Drugs that Target Neuropeptide and Neurotransmitter Systems. Expert Opinion on Investigational Drugs, 17, 321-325.
[164] Oh, S., Kim, K.S., Chung, Y.S., Shong, M. and Park, S.B. (2009) Anti-Obesity Agents: A Focused Review on the Structural Classification of Therapeutic Entities. Current Topics in Medicinal Chemistry, 9, 466-481.
[165] Breum, L. and Fernstrom, M.H. (2001) Drug-Induced Obesity. In: Bjorntorp, P. Ed., International Textbook of Obesity, Chapter 19, John Wiley & Sons, Ltd., Chichester, 269-281.
[166] Dent, R., Blackmore, A., Peterson, J., Habib, R., Kay, G.P., Gervais, A., Taylor, V. and Wells, G. (2012) Changes in Body Weight and Psychotropic Drugs: A Systematic Synthesis of the Literature. PLoS ONE, 7, e36889.
[167] Bernstein, J.G. (1987) Induction of Obesity by Psychotropic Drugs. Annals of the New York Academy of Sciences, 499, 203-215.
[168] Schwartz, T.L., Nihalani, N., Jindal, S., Virk, S. and Jones, N. (2004) Psychiatric Medication-Induced Obesity: A Review. Obesity Reviews, 5, 115-121.
[169] Martins, I.J., Wood, K.M., Fernandis, A.Z., Taddei, K. and Martins, R.N. (2013) Anti-Oxidative Acylcoa Cholesterol Acyltransferase Inhibitor Avasimibe Reduces the Impact of a High Cholesterol Diet on Brain Lipid Peroxidation in Mice. ADPD, Florence.
[170] Lai, C.S., Ho, M.H., Tsai, M.L., Li, S.M., Badmaev, V., Ho, C.T. and Pan, M.H. (2013) Suppression of Adipogenesis and Obesity in High-Fat Induced Mouse Model by Hydroxylated Polymethoxyflavones. Journal of Agricultural and Food Chemistry, 61, 10320-10328.
[171] Maeda, H., Hosokawa, M., Sashima, T., Murakami-Funayama, K. and Miyashita, K. (2009) Anti-Obesity and Anti-Diabetic Effects of Fucoxanthin on Diet-Induced Obesity Conditions in a Murine Model. Molecular Medicine Reports, 2, 897-902.
[172] Sugatani, J., Wada, T., Osabe, M., Yamakawa, K., Yoshinari, K. and Miwa, M. (2006) Dietary Inulin Alleviates Hepatic Steatosis and Xenobiotics-Induced Liver Injury in Rats Fed a High-Fat and High-Sucrose Diet: Association with the Suppression of Hepatic Cytochrome P450 and Hepatocyte Nuclear Factor 4α Expression. Drug Metabolism and Disposition, 34, 1677-1687.
[173] Mathur, S.J.N. (2003) Ginger and Its Role in Xenobiotic Metabolism. ICMR Bulletin, 33, 57-63.
[174] Jobu, K., Yokota, J., Yoshioka, S., Moriyama, H., Murata, S., Ohishi, M., Ukeda, H. and Miyamura, M. (2013) Effects of Goishi Tea on Diet-Induced Obesity in Mice. Food Research International, 54, 324-329.
[175] Muramkami, A. (2013) Modulation of Protein Quality Control Systems by Food Phytochemicals. Journal of Clinical Biochemistry and Nutrition, 52, 215-227.
[176] Imam, M.U. and Ismail, M. (2012) Effects of Brown Rice and White Rice on Expression of Xenobiotic Metabolism Genes in Type 2 Diabetic rats. International Journal of Molecular Sciences, 13, 8597-8608.
[177] Pan, M., Song, Y.L., Xu, J.M. and Gan, H.Z. (2006) Melatonin Ameliorates Nonalcoholic Fatty Liver Induced by High-Fat Diet in Rats. Journal of Pineal Research, 41, 79-84.
[178] Pfluger, P.T., Herranz, D., Velasco-Miguel, S., Serrano, M. and Tschop, M.H. (2008) Sirt1 Protects against High-Fat Diet-Induced Metabolic Damage. Proceedings of the National Academy of Sciences of the United States of America, 105, 9793-9798.
[179] Martins, I.J. and Fernando, W.M.A.D. (2014) High Fibre Diets and Alzheimer’s Disease. Food and Nutrition Sciences, 5, 410-424.
[180] Buler, M., Aatsinki, S.M., Skoumal, R. and Hakkola, J. (2011) Energy Sensing Factors PGC-1α and SIRT1 Modulate PXR Expression and Function. Biochemical Pharmacology, 82, 2008-2015.
[181] Suchankova, G., Nelson, L.E., Gerhart-Hines, Z., Kelly, M., Gauthier, M.S., Saha, A.K., Ido, Y., Puigserver, P. and Ruderman, N.B. (2009) Concurrent Regulation of AMP-Activated Protein Kinase and SIRT1 in Mammalian Cells. Biochemical and Biophysical Research Communications, 378, 836-841.
[182] Stanko, R.T., Reynolds, H.R., Hoyson, R., Janosky, J.E. and Wolf, R. (1994) Pyruvate Supplementation of a Low-Cholesterol, Low-Fat Diet: Effects on Plasma Lipid Concentrations and Body Composition in Hyperlipidemic Patients. American Journal of Clinical Nutrition, 59, 423-427.
[183] Kalman, D., Colker, C.M., Wilets, I., Roufs, J.B. and Antonio, J. (1999) The Effects of Pyruvate Supplementation on Body Composition in Overweight Individuals. Nutrition, 15, 337-340.
[184] Stanko, R.T., Tietze, D.L. and Arch, J.E. (1992) Body Composition, Energy Utilization, and Nitrogen Metabolism with a 4.25-MJ/d Low-Energy Diet Supplemented with Pyruvate. American Journal of Clinical Nutrition, 56, 630-635.
[185] Ojha, S., Goyal, S., Kumari, S. and Arya, D.S. (2012) Pyruvate Attenuates Cardiac Dysfunction and Oxidative Stress in Isoproterenol-Induced Cardiotoxicity. Experimental and Toxicologic Pathology, 64, 393-399.
[186] Izumi, Y., Katsuki, H. and Zorumski, C.F. (1997) Monocarboxylates (Pyruvate and Lactate) as Alternative Energy Substrates for the Induction of Long-Term Potentiation in Rat Hippocampal Slices. Neuroscience Letters, 232, 17-20.
[187] Kumashiro, N., Beddow, S.A., Vatner, D.F., et al. (2013) Targeting Pyruvate Carboxylase Reduces Gluconeogenesis and Adiposity and Improves Insulin Resistance. Diabetes, 62, 2183-2194.
[188] Martin, K.R. and Christy, L.A. (2010) Polyphenols as Dietary Supplements: A Double-Edged Sword. Nutrition and Dietary Supplements, 2, 1-12.
[189] Kimura, Y., Ito, H., Ohnishi, R. and Hatano, T. (2010) Inhibitory Effects of Polyphenols on Human Cytochrome P450 3A4 and 2C9 Activity. Food and Chemical Toxicology, 48, 429-435.
[190] Dai, G.L., He, L., Bu, P.L. and Wan, Y.J.Y. (2008) Pregnane X Receptor Is Essential for Normal Progression of Liver Regeneration. Hepatology, 47, 1277-1287.
[191] Calbet, J.A. and MacLean, D.A. (2002) Plasma Glucagon and Insulin Responses Depend on the Rate of Appearance of Amino Acids after Ingestion of Different Protein Solutions in Humans. Journal of Nutrition, 132, 2174-2182.
[192] Floyd, J.C., Fajans, S.S., Conn, J.W., Knopf, R.F. and Rull, J. (1966) Stimulation of Insulin Secretion by Amino Acids. Journal of Clinical Investigation, 45, 1487-1502.
[193] Zhang, Y.Y., Guo, K.Y., LeBlanc, R.E., Loh, D., Schwartz, G.J. and Yu, Y.H. (2007) Increasing Dietary Leucine Intake Reduces Diet-Induced Obesity and Improves Glucose and Cholesterol Metabolism in Mice via Multimechanisms. Diabetes, 56, 1647-1654.
[194] Guo, K.Y., Yu, Y.H., Hou, J. and Zhang, Y.Y. (2010) Chronic Leucine Supplementation Improves Glycemic Control in Etiologically Distinct Mouse Models of Obesity and Diabetes Mellitus. Nutrition & Metabolism, 7, 57.
[195] Torres-Leal, F.L., Fonseca-Alaniz, M.H., Teodoro, G.F.R., et al. (2011) Leucine Supplementation Improves Adiponectin and Total Cholesterol Concentrations Despite the Lack of Changes in Adiposity or Glucose Homeostasis in Rats Previously Exposed to a High-Fat Diet. Nutrition & Metabolism, 8, 62.
[196] Su, Y., Lam, T.K.T., He, W., Pocai, A., Bryan, J., Aguilar-Bryan, L. and Gutiérrez-Juárez, R. (2012) Hypothalamic Leucine Metabolism Regulates Liver Glucose Production. Diabetes, 61, 85-93.
[197] Zampieri, T.T., Pedroso, J.A.B., Furigo, I.C., Tirapegui, J. and Donato, J. (2013) Oral Leucine Supplementation Is Sensed by the Brain But Neither Reduces Food Intake Nor Induces an Anorectic Pattern of Gene Expression in the Hypothalamus. PLoS ONE, 8, e84094.
[198] (2014) REDD1—Linking GPCRs and mTOR. Journal of Cell Science, 127, e0405.
[199] Laplante, M. and Sabatini, D.M. (2012) mTOR Signaling in Growth Control and Disease. Cell, 149, 274-293.
[200] Hsu, S.Y., Kudo, M., Chen, T., Nakabayashi, K., Bhalla, A., van der Spek, P.J., van Duin, M. and Hsueh, A.J.W. (2000) The Three Subfamilies of Leucine-Rich Repeat-Containing G Protein-Coupled Receptors (LGR): Identification of LGR6 and LGR7 and the Signaling Mechanism for LGR7. Molecular Endocrinology, 14, 1257-1271.
[201] Bjenning, C., Al-Shamma, H., Thomsen, W., Leonard, J. and Behan, D. (2004) G Protein-Coupled Receptors as Therapeutic Targets for Obesity and Type 2 Diabetes. Current Opinion in Investigational Drugs, 5, 1051-1062.
[202] Ghosh, H.S., McBurney, M. and Robbins, P.D. (2010) SIRT1 Negatively Regulates the Mammalian Target of Rapamycin. PLoS ONE, 5, e9199.
[203] Liu, M.L. and Liu, F. (2011) Resveratrol Inhibits mTOR Signaling by Targeting DEPTOR. Communicative & Integrative Biology, 4, 382-384.
[204] Walker, D.K. (2006) Potential Importance of Leucine in Treatment of Obesity and the Metabolic Syndrome. Journal of Nutrition, 136, 319S-23S.
[205] Knapik, J., Meredith, C., Jones, B., Fielding, R., Young, V. and Evans, W. (1991) Leucine Metabolism during Fasting and Exercise. Journal of Applied Physiology, 70, 43-47.
[206] Layman, D.K. (2002) Role of Leucine in Protein Metabolism during Exercise and Recovery. Canadian Journal of Applied Physiology, 27, 646-662.
[207] Crowe, M.J., Weatherson, J.N. and Bowden, B.F. (2006) Effects of Dietary Leucine Supplementation on Exercise Performance. European Journal of Applied Physiology, 97, 664-672.
[208] Roberts, C.K. and Barnard, R.J. (1985) Effects of Exercise and Diet on Chronic Disease. Journal of Applied Physiology, 98, 3-30.
[209] Vinciguerra, M., Fulco, M., Ladurner, A., Sartorelli, V. and Rosenthal, N. (2010) SirT1 in Muscle Physiology and Disease: Lessons from Mouse Models. Disease Models & Mechanisms, 3, 298-303.
[210] Pardo, P.S. and Boriek, A.M. (2011) The Physiological Roles of Sirt1 in Skeletal Muscle. Aging (Albany NY), 3, 430-437.
[211] Guichelaar, M.M. and Charlton, M.R. (2014) Decreased Muscle Mass in Nonalcoholic Fatty Liver Disease: New Evidence of a Link between Growth Hormone and Fatty Liver Disease? Hepatology.
[212] Flannery, C., Dufour, S., Rabøl, R., Shulman, G.I. and Petersen, K.F. (2012) Skeletal Muscle Insulin Resistance Promotes Increased Hepatic de Novo Lipogenesis, Hyperlipidemia, and Hepatic Steatosis in the Elderly. Diabetes, 61, 2711-2717.
[213] Gachona, F., Leuenberger, N., Claudel, T., Gos, P., Jouffe, C., Fleury Olela, F., de Mollerat du Jeu, X., Wahli, W. and Schibler, U. (2011) Proline- and Acidic Amino Acid-Rich Basic Leucine Zipper Proteins Modulate Peroxisome Proliferator-Activated Receptor α (PPARα) Activity. Proceedings of the National Academy of Sciences of the United States of America, 108, 4794-4799.
[214] Gachon, F., Olela, F.F., Schaad, O., Descombes, P. and Schibler, U. (2006) The Circadian PAR-Domain Basic Leucine Zipper Transcription Factors DBP, TEF, and HLF Modulate Basal and Inducible Xenobiotic Detoxification. Cell Metabolism, 4, 25-36.
[215] Kritchevsky, D. (1985) Influence of Dietary Fiber on Xenobiotics. In: Xenobiotic Metabolism: Nutritional Effects, ACS Symposium Series, Vol. 277, Chapter 5, 51-60.
[216] Debethizy, J.D. and Goldstein, R.S. (1985) The Influence of Fermentable Dietary Fiber on the Disposition and Toxicity of Xenobiotics. In: Xenobiotic Metabolism: Nutritional Effects, ACS Symposium Series, Vol. 277, Chapter 4, 37-50.
[217] Martins, I.J. (2014) Nutrition and Genotoxic Stress Contributes to Diabetes and Neurodegenerative Diseases such as Parkinson’s Disease and Alzheimer’s Disease. Editors Bentham ebooks 2013, In: Atta-ur-Rahman, Ed., Frontiers in Clinical Drug Research-CNS and Neurological Disorders, Vol. 3, Chapter 1, 1-40.
[218] Wielgus, A.R. and Roberts, J.E. (2012) Retinal Photodamage by Endogenous and Xenobiotic Agents. Photochemistry Photobiology, 88, 1320-1345.
[219] Cheung, N. and Wong, T.Y. (2007) Obesity and Eye Diseases. Survey of Ophthalmology, 52, 180-195.

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