What is obesity, and why does it matter?

Obesity is a highly complex and progressive chronic disease that impairs health, characterised by abnormal and/or excessive body fat.¹

Obesity is also a driver of multiorgan metabolic dysfunction. Addressing obesity can therefore help prevent, delay progression, or promote regression of other interconnected cardiovascular, renal, and metabolic conditions, including complications related to the heart, kidneys, and liver.

Prof. Carel le Roux outlines how to effectively treat obesity

SC-GB-03715 Metabolism - What biological mechanisms drive obesity

How many people are living with obesity?

Approximately 1 billion people worldwide are currently living with obesity.² By 2035, it is estimated that obesity will affect 1.5 billion people globally, highlighting it as a major global health challenge.²

Expand all

2035 estimated prevalence of obesity in adults

People living with obesity often have other obesity-related complications that affect their life expectancy.⁴

Global prevalence of obesity-related health complications

*Note that estimates may be even higher when obesity is defined using anthropometric measures, such as waist circumference, rather than BMI.¹³

BMI, body mass index; MASH, metabolic dysfunction-associated steatohepatitis; MASLD, metabolic dysfunction-associated steatotic liver disease.

What factors lead to obesity?

Expand all

The underlying cause of obesity is dysregulation of the body’s energy balance. When a person’s energy input outweighs their energy expenditure, this results in weight gain.^14-17

Obesity cannot be managed by just advising patients to “eat less, move more,” as human biology is engineered by evolution to vigorously defend weight by a complex interplay of neural, hormonal, and metabolic pathways.¹⁸

The brain’s control of appetite is influenced by various control systems, shaping how hunger, cravings, satiation and satiety are experienced and managed.^16,18,19

Homeostatic control

Eating based on the body’s energy needs. Regulated by the serotonin system, melanocortin system, and noradrenaline system.

Hedonic control

Eating based on palatability. This is driven by the wanting, liking, and pleasure of food, even in the absence of hunger.

Cognitive control/executive function

Conscious food-related decision-making, such as eating from emotional hunger or stress.

The primary region of the brain that regulates homeostatic control of body weight and appetite is called the arcuate nucleus, which is located in the hypothalamus.¹⁸

The arcuate nucleus consists of two distinct groups of neurons:^18,20

Neurons that co-express orexigenic peptides

These neurons respond to low negative energy balance to increase appetite and decrease energy expenditure (AgRP/NPY pathway).

Neurons that express anorexigenic peptides

These neurones decrease appetite and increase energy expenditure (POMC/MC4R pathway).

AgRP, agouti-related peptide; MC4R, melanocortin-4 receptor; NPY, neuropeptide Y; POMC, pro-opiomelanocortin.

Endocrine control of appetite

There are several hormones that help the brain regulate appetite. These hormones are secreted from various locations within the body and play a unique role in appetite regulation.^21-24

GLP-1, glucagon-like peptide 1.

What comorbidities are associated with obesity?

People living with obesity are at increased risk of developing other medical conditions. Obesity is associated with >200 comorbidities and can affect every organ system, driving multiorgan dysfunction.²⁵ This spectrum of diseases can significantly impact quality of life and life expectancy.^4,14

Expand all

Obesity is a gateway disease to a range of mechanical, mental and metabolic complications – the 3 M’s. This includes metabolic dysfunction-associated steatotic liver disease (MASLD), cardiovascular disease and type 2 diabetes.²⁶

Obesity is associated with multiple comorbidities^27-32

*Including breast, colorectal, endometrial, esophageal, kidney, ovarian, pancreatic, and prostate cancer.

CV, cardiovascular; GERD, gastroesophageal reflux disease; MASH, metabolic dysfunction-associated steatohepatitis; MASLD, metabolic dysfunction-associated steatotic liver disease; T2D, type 2 diabetes.

In people living with obesity, excess visceral fat can fuel fat spillover and fat deposition in various organs of the body, such as:^33-35

MASLD, metabolic dysfunction-associated steatotic liver disease.

In particular, excess visceral fat and liver fat promote the release of adipokines and pro-inflammatory cytokines (such as TNF‑α [Tumor Necrosis Factor alpha] and IL‑6 [Interleukin-6]), leading to chronic low-grade inflammation and contributing to impaired liver function, and metabolic dysfunction.³⁶

Excess visceral fat and excess liver fat have wide-reaching consequences^36-41

CV, cardiovascular; MASH, metabolic dysfunction-associated steatohepatitis; MASLD, metabolic dysfunction-associated steatotic liver disease; T2D, type 2 diabetes.

Reducing visceral fat and liver fat accumulation is therefore important for managing obesity, as well as for improving overall metabolic health.³⁶

Overview

Obesity & Liver Health

Back to overview

Obesity

Burden of Obesity

Bowman-Busato J, et al. Providing a common language for obesity: the European Association for the Study of Obesity obesity taxonomy. Int J Obes (Lond). 2025;49:182-191.
World Obesity Federation. World Obesity Atlas 2024. 2024. Available at: https://data.worldobesity.org/publications/WOF-Obesity-Atlas-v7.pdf. Last accessed: April 2026.
World Obesity Federation. World Obesity Atlas 2023. 2023. Available at: https://www.worldobesity.org/resources/resource-library/world-obesity-atlas-2023. Last accessed: April 2026.
Vallis M. Quality of life and psychological well-being in obesity management: improving the odds of success by managing distress. Int J Clin Pract. 2016;70:196-205.
Younossi ZM, et al. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology. 2023;77:1335-1347.
GBD 2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2023;402:203-234.
Roth GA, et al. Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study. J Am Coll Cardiol. 2020;76:2982-3021.
Jager KJ, et al. A single number for advocacy and communication-worldwide more than 850 million individuals have kidney diseases. Kidney Int. 2019;96:1048-1050.
Alicic RZ, et al. Diabetic Kidney Disease: Challenges, Progress, and Possibilities. Clin J Am Soc Nephrol. 2017;12:2032-2045.
Yanai H, et al. Metabolic-Dysfunction-Associated Steatotic Liver Disease-Its Pathophysiology, Association with Atherosclerosis and Cardiovascular Disease, and Treatments. Int J Mol Sci. 2023;24:15473.
Quek J, et al. Global prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in the overweight and obese population: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2023;8:20-30.
Grant B, et al. Managing obesity in people with type 2 diabetes. Clin Med (Lond). 2021;21:e327-e331.
Shrestha R, et al. BMI, waist to height ratio and waist circumference as a screening tool for hypertension in hospital outpatients: a cross-sectional, non-inferiority study. BMJ Open. 2021;11:e050096.
Koskinas KC, et al. Obesity and cardiovascular disease: an ESC clinical consensus statement. Eur Heart J. 2024;45:4063-4098.
Scientific Advisory Committee on Nutrition. Dietary Reference Values for Energy. 2011. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/339317/SACN_Dietary_Reference_Values_for_Energy.pdf. Last accessed: April 2026.
Thorp AA, Schlaich MP. Relevance of Sympathetic Nervous System Activation in Obesity and Metabolic Syndrome. J Diabetes Res. 2015;2015:1-11.
Hussain SS, Bloom SR. The regulation of food intake by the gut-brain axis: implications for obesity. Int J Obes (Lond). 2013;37:625-633.
Kumar RB, et al. Understanding the pathophysiologic pathways that underlie obesity and options for treatment. Expert Rev Endocrinol Metab. 2021;16:321-338.
Cifuentes L, Acosta A. Homeostatic regulation of food intake. Clin Res Hepatol Gastroenterol. 2022;46:101794.
Grandone A, et al. New treatment modalities for obesity. Best Pract Res Clin Endocrinol Metab. 2018;32:535-549.
Del Prato S, et al. The incretin/glucagon system as a target for pharmacotherapy of obesity. Obes Rev. 2022;23:e13372.
Osto M, et al. Modulation of the satiating effect of amylin by central ghrelin, leptin and insulin. Physiol Behav. 2007;91:566-572.
Steinert RE, et al. Ghrelin, CCK, GLP-1, and PYY(3-36): Secretory Controls and Physiological Roles in Eating and Glycemia in Health, Obesity, and After RYGB. Physiol Rev. 2017;97:411-463.
Pocai A. Action and therapeutic potential of oxyntomodulin. Mol Metab. 2014;3:241-251.
Dabbous F, et al. Estimating the association and timing of occurrence between obesity and related comorbidity outcomes in a real-world setting: A cohort study in the United States. Clin Obes. 2025;15:e70026.
Lingvay I, et al. Obesity in adults. Lancet. 2024;404:972-987.
Sharma AM. M, M, M & M: a mnemonic for assessing obesity. Obes Rev. 2010;11:808-809.
Guh DP, et al. The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health. 2009;9:88.
Luppino FS, et al. Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry. 2010;67:220-229.
Simon GE, et al. Association between obesity and psychiatric disorders in the US adult population. Arch Gen Psychiatry. 2006;63(7):824-830.
Church TS, et al. Association of cardiorespiratory fitness, body mass index, and waist circumference to nonalcoholic fatty liver disease. Gastroenterology. 2006;130:2023-2030.
Li C, et al. Prevalence of self-reported clinically diagnosed sleep apnea according to obesity status in men and women: National Health and Nutrition Examination Survey, 2005-2006. Prev Med. 2010;51:18-23.
Janochova K, et al. Visceral fat and insulin resistance - what we know? Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2019;163:19-27.
Bays H. Central obesity as a clinical marker of adiposopathy; increased visceral adiposity as a surrogate marker for global fat dysfunction. Curr Opin Endocrinol Diabetes Obes. 2014;21:345-351.
Hua Y, et al. Perirenal fat as a potential marker and therapeutic target for metabolic syndrome: insights from a multicenter randomized controlled trial. Front Endocrinol (Lausanne). 2025;16:1557701.
Bansal S, et al. Visceral fat: A key mediator of NAFLD development and progression. Hum Nutr Metab. 2023;33:200210.
Younossi ZM, et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64:73-84.
Fabbrini E, et al. Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology. 2010;51:679-689.
Ratziu V, et al. Current efforts and trends in the treatment of NASH. J Hepatol. 2015;62:S65-S75.
Ndumele CE, et al. A Synopsis of the Evidence for the Science and Clinical Management of Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Scientific Statement From the American Heart Association. Circulation. 2023;148:1636-1664.
Islam MS, et al. The interplay of factors in metabolic syndrome: understanding its roots and complexity. Mol Med. 2024;30:279.