What is the pathophysiology of obesity?

Updated: Feb 16, 2021
  • Author: Alan A Saber, MD, MS, FACS, FASMBS; Chief Editor: John Geibel, MD, MSc, DSc, AGAF  more...
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Obesity occurs as the result of an imbalance between energy expenditure and caloric intake. This imbalance has been thought to be under genetic and environmental influence. The discovery of immunologic abnormalities in obesity that are related to the leptin-proopiomelanocortin system and elevated tumor necrosis factor alpha (TNF-α) brought a new perspective to the understanding of obesity.

Leptin (from Greek leptos, "thin") is a hormone made primarily in adipocytes. The circulating leptin levels reflect the amount of stored body fat. Leptin is a negative feedback signal that acts on the hypothalamus to alter the expression of several neuroendocrine peptides that regulate energy intake and expenditure. Central resistance to leptin is a prominent feature of obesity.

Increased leptin levels in individuals who are obese are independent of the lipid profile but strongly correlate with the BMI. Leptin exhibits direct effects on monocytes that results in secretion of the interleukin (IL)-1 receptor antagonist (IL-1RA). This cytokine antagonist has anti-inflammatory properties. Although leptin treatment works very well in patients who are leptin-deficient, the use of leptin in patients who are obese and who already have high levels of leptin has shown limited efficacy.

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