Pathophysiology of Obesity: An Extensive Review

Bidisha Das; Kazi Layla Khaled

doi:10.35652/IGJPS.2024.14001

Authors

Bidisha Das Department of Home Science, University of Calcutta, 20B Judges Court Road, Kolkata-700027, West Bengal, India
Kazi Layla Khaled Department of Home Science, University of Calcutta, 20B Judges Court Road, Kolkata-700027, West Bengal, India

DOI:

https://doi.org/10.35652/IGJPS.2024.14001

Keywords:

Obesity, Pathophysiology, Neural, Genetic Epigenetic

Abstract

Obesity refers to a medical condition where excess adipose tissue accumulates in the body to such an amount that it leads to more than 20 percent of the ideal body weight. Obesity develops due to a chronic energy imbalance between calorie consumption and expenditure. Obesity enhances the chance of different types of diseases such as cardiovascular diseases, Type 2 diabetes, gall stones, obstructive sleep apnea, specific types of cancer, osteoarthritis, depression, obstetrical risks, gout and so on. Excess body fat causes breathlessness on mild to moderate exertion. A combination of different factors such as excessive food intake, especially fast food, sedentary life style, and genetic factors increases obesity risk. To control obesity, it is imperative to create efficient therapy plans and proactive initiatives, both of which will depend on a thorough knowledge of the pathophysiology of obesity. This review paper summarizes the pathophysiology behind obesity, which mainly includes endocrinal, genetic, epigenetic, neural, metabolic, lifestyle factors, micro-environmental factors. Understanding the pathophysiology of the rising trend of obesity epidemic requires a thorough understanding of the systems which can control energy balance in our body. Scientists are working to gain deep knowledge on the pathophysiology of obesity in order to develop effective therapy strategies for this condition, as well as to better influence the development of public policy in favour of public welfare and obesity awareness in ways that can minimise the detrimental effects of obesity on community health and economy.

Metrics

Metrics Loading ...

References

Ofei, F. Obesity - A Preventable Disease. Ghana. Med. J., 2005; 39(3): 98–101.

Schwartz, M.W. et al. Obesity Pathogenesis: An Endocrine Society Scientific Statement. Endocr. Rev., 2017; 38(4): 267–296.

Kinlen, D., Cody, D., Shea, D.O'. Complications of obesity. QJM Int. J. Med., 2018; 111(7): 437–443.

https://www.who.int/health-topics/obesity#tab=tab_1 visited on 11.08.22.

Ahirwar, R., Mondal, P.R. Prevalence of obesity in India: A systematic review. Diabetes Metab Syndr., 2019; 13(1): 318-321.

https://www.frontiersin.org/articles/10.3389/fendo.2021.706978/full#B3 visited on 11.08.22.

https://en.wikipedia.org/wiki/Pathophysiology_of_obesity visited on 11.08.22.

Flier, J.S. Obesity wars: molecular progress confronts an expanding epidemic. Cell., 2004; 116(2): 337–350.

Hall, J.E., Guyton, A.C. Textbook of Medical Physiology, 12th ed.; ELSEVIER INC: USA, 2010.

Obradovic, M. et al. Leptin and Obesity: Role and Clinical Implication. Front. Endocrinol., 2021; Volume 12: Article 585887.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762294/ visited on 12/8/22

Jais, A., Brüning, J.C. Arcuate Nucleus-Dependent Regulation of Metabolism—Pathways to Obesity and Diabetes Mellitus. Endocr Rev., 2022; 43(2): 314–328.

https://escholarship.org/content/qt54b1p00d/qt54b1p00d_noSplash_4efbe26b4324bd65d558c047708aa560.pdf?t=ptt38k#:~:text=Signals%20from%20the%20GI%20tract,involved%20in%20meal%20termina%2D%20tion. visited on 12/8/22

Sembulingam, K., Sembulingam, P. Essentials of Medical Physiology, 6th ed.; Jaypee Brothers Medical Publishers (P) Ltd: New Delhi, 2012.

Flier, J.S. Clinical review 94: What's in a name? In search of leptin's physiologic role. J. Clin. Endocrinol. Metab., 1998; 83(5): 1407–1413.

Farooqi, I.S. et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N. Engl. J. Med., 1999; 341(12): 879–884.

Flak, J.N., Myers, M.G., Jr. Minireview: CNS Mechanisms of Leptin Action. Mol Endocrinol., 2016; 30(1): 3–12.

Myers, M.G. Jr. et al. Challenges and opportunities of defining clinical leptin resistance. Cell. Metab., 2012; 15(2): 150–156.

Nunziata, A. et al. Estimated prevalence of potentially damaging variants in the leptin gene. Mol. Cell. Pediatr., 2017; 4(1): 10.

Baumann, H. et al. The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors. Proc Natl Acad Sci USA., 1996; 93: 8374–8378.

Banks, A.S., Davis, S.M., Bates, S.H., Myers, M.G., Jr. Activation of downstream signals by the long form of the leptin receptor. J Biol Chem., 2000; 275: 14563–14572.

Dhillon, H. et al. Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis. Neuron.; 2006; 49: 191–203.

Hawke, Z., Ivanov, T.R., Bechtold, D.A., Dhillon, H., Lowell, B.B., Luckman, S.M. PACAP neurons in the hypothalamic ventromedial nucleus are targets of central leptin signaling. J Neurosci.; 2009; 29: 14828–14835.

Leinninger , G.M. et al. Leptin acts via leptin receptor-expressing lateral hypothalamic neurons to modulate the mesolimbic dopamine system and suppress feeding. Cell Metab.; 2009; 10: 89–98.

Müller, T.D. et al. Ghrelin. Mol. Metab., 2015; 4(6): 437–460.

Burger, K.S., Berner, L.A. A functional neuroimaging review of obesity, appetitive hormones and ingestive behavior. Physiol. Behav., 2014; 136: 121–127.

Davenport, A.P. et al. International Union of Pharmacology. LVI. Ghrelin receptor nomenclature, distribution, and function. Pharmacol. Rev., 2005; 57(4): 541–546.

Pradhan, G., Samson, S.L., Sun, Y. Ghrelin: much more than a hunger hormone. Curr. Opin. Clin. Nutr. Metab. Care., 2013; 16(6): 619–624.

Wiedmer, P., Nogueiras, R., Broglio, F., D'Alessio, D., Tschöp, M.H. Ghrelin, obesity and diabetes. Nat. Clin. Pract. Endocrinol. Metab., 2007; 3(10): 705–712.

Page, A.J. et al. Ghrelin selectively reduces mechanosensitivity of upper gastrointestinal vagal afferents. Am. J. Physiol. Gastrointest. Liver. Physiol., 2007; 292(5): G1376-1384.

Beccuti, G., Pannaina, S. Sleep and obesity. Curr. Opin. Clin. Nutr. Metab. Care., 2011; 14(4): 402–412.

Voshol, P.J. et al. In muscle-specific lipoprotein lipase-overexpressing mice, muscle triglyceride content is increased without inhibition of insulin-stimulated whole-body and muscle-specific glucose uptake. Diabetes., 2001; 50(11): 2585–2590.

Okubo, M. et al. A novel complex deletion-insertion mutation mediated by Alu repetitive elements leads to lipoprotein lipase deficiency. Mol. Genet. Metab., 2007; 92(3): 229–233.

Ferreira, L.D., Pulawa, L.K., Jensen, D.R., Eckel, R.H. Overexpressing human lipoprotein lipase in mouse skeletal muscle is associated with insulin resistance. Diabetes., 2001; 50(5): 1064–1068.

Delezie, J. et al. The nuclear receptor REV-ERBα is required for the daily balance of carbohydrate and lipid metabolism. FASEB. J., 2012; 26(8): 3321–3335.

Oussaada, S.M. et al. The pathogenesis of obesity. Metab. Clin. Exp., 2019; 92: 26–36.

Bray, G.A. Etiology and pathogenesis of obesity. Clin. Cornerstone., 1999; 2(3): 1-15.

Cavaillé, J. et al. Identification of brain-specific and imprinted small nucleolar RNA genes exhibiting an unusual genomic organization. Proc. Natl. Acad. Sci. U.S.A., 2000; 97(26): 14311–14316.

Buiting, K. et al. Inherited microdeletions in the Angelman and Prader-Willi syndromes define an imprinting centre on human chromosome 15. Nat. Genet., 1995; 9(4): 395–400.

Mlinar, B., Marc, J., Janez, A., Pfeifer, M. Molecular mechanisms of insulin resistance and associated diseases. Clin. Chim. Acta., 2007; 375(1-2): 20-35.

Dulloo, A.G., Seydoux, J., Jacquet, J. Adaptive thermogenesis and uncoupling proteins: a reappraisal of their roles in fat metabolism and energy balance. Physiol. Behav., 2004; 83(4): 587-602.

Casteilla, L., Cousin, B., Carmona, M. PPARs and Adipose Cell Plasticity. PPAR. Res., 2007; 2007: 68202.

Hesse, S. et al. Association of central serotonin transporter availability and body mass index in healthy Europeans. Eur. Neuropsychopharmacol., 2014; 24(8): 1240–1247.

La Fleur, S.E., Serlie, M.J. The interaction between nutrition and the brain and its consequences for body weight gain and metabolism; studies in rodents and men. Best. Pract. Res. Clin. Endocrinol. Metab., 2014; 28(5): 649–659.

Gluskin, B.S., Mickey, B.J. Genetic variation and dopamine D2 receptor availability: a systematic review and meta-analysis of human in vivo molecular imaging studies. Transl. Psychiatry., 2016; 6: e747.

Noble, E.P. et al. D2 dopamine receptor gene and obesity. Int. J. Eat. Disord., 1994; 15(3): 205–217.

Bird, A. Perceptions of epigenetics. Nature., 2007; 447(7143): 396–398.

Reik, W., Walter, J. Imprinting mechanisms in mammals. Curr. Opin. Genet. Dev., 1998; 8(2): 154–164.

Butler, M.G. Genomic imprinting disorders in humans: a mini-review. J. Assist. Reprod. Genet., 2009; 26(9–10): 477–486.

Haig, D., Graham, C. Genomic imprinting and the strange case of the insulin-like growth factor II receptor. Cell., 1991; 64(6): 1045–1046.

Shapira, N.A., Lessig, M.C., He, A.G., James, G.A., Driscoll, D.J., Liu, Y. Satiety dysfunction in Prader–Willi syndrome demonstrated by fMRI. J. Neurol. Neurosurg. Psychiatry., 2005; 76(2): 260–262.

Panigrahi, T.G., Panigrahi, S., Wiechec, E., Los, M. Obesity: Pathophysiology and Clinical Management. Curr. Med. Chem., 2009; 16(1): 506-521.

Mineur, Y.S. et al. Nicotine decreases food intake through activation of POMC neurons. Science. 2011; 332(6035): 1330–1332.