After metabolic bariatric surgery in people with obesity, levels of two hormones called oxyntomodulin and FGF21 rise within four weeks, and this rise is linked to greater weight loss one year later.
Mechanism
Synthesis from 1 study
After surgery, the body releases hormones that tell fat cells to break down stored fat. These fat molecules travel to the liver, which uses them to make more of a hormone called FGF21. FGF21 then tells certain fat tissues to start burning energy as heat instead of storing it, which helps the body...
Most probable mechanism
After surgery, the body releases more of two hormones called OXM and FGF21. These hormones tell fat cells to break down stored fat into fatty acids, which then travel to the liver. The liver uses those fatty acids to produce energy and a byproduct called ketones, which signals the liver to release even more FGF21. This FGF21 then tells brown fat and some white fat to start burning energy as heat instead of storing it, which helps the body lose weight over time.
Oxyntomodulin (OXM) activates glucagon receptors on white adipose tissue, triggering intracellular cAMP/PKA signaling that phosphorylates hormone-sensitive lipase and initiates triglyceride breakdown into free fatty acids and glycerol.
Free fatty acids released from adipose tissue are taken up by the liver, where they activate PPARα and increase expression of CPT1a, driving mitochondrial fatty acid oxidation and ketogenesis.
Hepatic ketogenesis and glucagon receptor signaling upregulate FGF21 gene expression and secretion, elevating circulating FGF21 levels.
Elevated FGF21 acts on brown adipose tissue and white adipose tissue to induce UCP1 expression and thermogenic gene programs, increasing energy expenditure.
Increased energy expenditure from thermogenic adipose tissue, combined with reduced fat storage, leads to sustained weight loss over one year.
Less supported by current evidence, but not ruled out
After surgery, fat tissue releases more adiponectin, which signals the liver to burn more fat and produce more FGF21, helping the body lose weight by increasing energy use.
Oxyntomodulin (OXM) and related signals increase adiponectin secretion from white adipose tissue.
Adiponectin binds to receptors on hepatocytes, activating AMPK and PPARα pathways to enhance fatty acid oxidation and suppress lipid synthesis.
Enhanced hepatic fatty acid oxidation and metabolic stress increase FGF21 production and secretion.
Elevated FGF21 promotes thermogenesis in brown and beige fat, contributing to long-term energy imbalance and weight loss.
Fat breakdown after surgery attracts special immune cells that release signals telling white fat to behave like heat-burning fat, helping the body lose weight.
Free fatty acids released from adipose tissue act as chemoattractants for eosinophils and type 2 innate lymphoid cells.
Infiltrating immune cells secrete IL-4 and IL-13, which polarize macrophages to an M2 phenotype and induce UCP1 expression in white adipocytes.
Beiging of white adipose tissue increases local energy expenditure and contributes to systemic metabolic improvement.
Evidence from Studies
Supporting (1)
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The dual GLP-1/glucagon receptor agonist G49 mimics bariatric surgery effects by inducing metabolic rewiring and inter-organ crosstalk
Contradicting (0)
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