Interaction Between Leptin and Gut Hormones in the Regulation of Food Intake and Body Weight pp. 187-208
Authors: (Tooru M. Mizuno, Tooru M. Mizuno, Ph.D., Department of Physiology, University of Manitoba, Winnipeg, Manitoba, R3E 0J9, Canada, and others)
Abstract: Leptin is the adipocyte-derived hormone which is released into the circulation in direct proportion to adiposity and participates in the long-term regulation of body weight. Leptin treatment is effective in reversing metabolic impairments in leptin-deficient mice and humans. However, the majority of human obesity is associated with elevated circulating leptin levels and leptin resistance, limiting the weight-lowering effect of leptin. Therefore, establishment of a strategy to reverse leptin resistance is urgent. Meal-associated gastrointestinal hormones have been proven to be effective in reducing short-term food intake. However, the effect of gastrointestinal hormones on long-term food intake and body weight is limited in both magnitude and duration in general. Leptin and gastrointestinal satiety-promoting hormones reduce food intake and body weight by activating the central nervous system (CNS) cells through their synergistic interaction. Combined treatment of leptin and gastrointestinal hormone produces greater reductions in food intake and body weight compared to the treatment with leptin alone or gastrointestinal hormone alone in both normal and leptin-resistant animals. Pre-treatment with gastrointestinal hormone restores leptin-induced activation of CNS signaling in obese leptin-resistant animals. Thus, leptin amplifies feeding inhibition and neural activation produced by gut-derived hormones, suggesting that leptin may increase the efficacy of gastrointestinal meal-related signals. Alternatively, gut-derived hormones may enhance responsiveness to leptin in CNS cells. It is proposed that the interactions between leptin and gastrointestinal hormones participate in the regulation of both short-term feeding and long-term body weight and that the combination treatment of leptin and gastrointestinal hormones is an effective strategy for the treatment of obesity, in particular leptin-resistant obesity.
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