Altered gut and adipose tissue hormones in overweight and obese individuals: cause or consequence?

Abstract

The aim of this article is to review the research into the main peripheral appetite signals altered in human obesity, together with their modifications after body weight loss with diet and exercise and after bariatric surgery, which may be relevant to strategies for obesity treatment. Body weight homeostasis involves the gut-brain axis, a complex and highly coordinated system of peripheral appetite hormones and centrally mediated neuronal regulation. The list of peripheral anorexigenic and orexigenic physiological factors in both animals and humans is intimidating and expanding, but anorexigenic glucagon-like peptide 1 (GLP-1), cholecystokinin (CCK), peptide YY (PYY) and orexigenic ghrelin from the gastrointestinal tract, pancreatic polypeptide (PP) from the pancreas and anorexigenic leptin from adiposites remain the most widely studied hormones. Homeostatic control of food intake occurs in humans, although its relative importance for eating behaviour is uncertain, compared with social and environmental influences. There are perturbations in the gut-brain axis in obese compared with lean individuals, as well as in weight-reduced obese individuals. Fasting and postprandial levels of gut hormones change when obese individuals lose weight, either with surgical or with dietary and/or exercise interventions. Diet-induced weight loss results in long-term changes in appetite gut hormones, postulated to favour increased appetite and weight regain while exercise programmes modify responses in a direction expected to enhance satiety and permit weight loss and/or maintenance. Sustained weight loss achieved by bariatric surgery may in part be mediated via favourable changes to gut hormones. Future work will be necessary to fully elucidate the role of each element of the axis, and whether modifying these signals can reduce the risk of obesity.

Figure 1

GLP-1 responses to a liquid test meal in 19 normal-weight and 20 obese subjects. Reproduced with permission.

Figure 2

PYY responses 90 min after each of six test meals of increasing caloric content in 20 obese and 20 normal-weight subjects. *P<0.05 (unpaired t-test). Reproduced with permission.

Figure 3

Ghrelin responses to a test meal in 10 normal-weight and 13 severely obese women. Ghrelin levels were significantly higher. *(P⩽0.05) in normal-weight women at baseline (P=0.001) and at 15 (P=0.001), 60 (P=0.032) and 120 (P=0.044) min postprandially. Reproduced with permission.