# Exercise Suppresses Appetite in Obesity: A Biochemical, Metabolic, and Molecular Approach
## 2 Exercise and Appetite-Regulatory Hormones  
Adipose tissue is a metabolically active organ that undergoes structural and functional changes in response to dietary changes and food intake [41]. Most anti-obesity treatments address the suppression of appetite to curb excess energy intake [42; 43], with changes in lifestyle and regular exercise being effective non-pharmacological interventions in managing adiposity and related diseases [44]. Regular physical activity expedites weight management by increasing energy expenditure and regulating appetite hormones (orexigenic and anorexiapic) [23; 45], including leptin, ghrelin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY), glucose-dependent insulinotropic polypeptide (GIP), and cholecyst-tokinin (CCK) [46]. These hormones are synthetized and secreted from peripheral tissues (intestine and adipocytes [6]) and interact with brain centers (hypothalamus) monitoring and regulating feeding and satiety behaviors [47]. Although a sedentary lifestyle disturbs the mechanisms responsible for appetite regulation [48], exercise regulates appetite and appetite-regulating hormones in sedentary individuals with obesity [30; 49]. In this context, three different intensities of resistance training improve body weight and fat; reduce leptin, CCK, and GIP; and increase ghrelin, adiponectin, PYY, and GLP-1 [50]. However, the effects of endurance training on these appetite hormones may be different. Ghrelin is released by gastric oxyntic cells in response to fasting [51]. Plasma levels of the orexigenic hormone ghrelin are reduced in obesity [52] (Figure 1). Resistance exercise increases ghrelin levels, which may be mediated in part by catecholamines in an exercise-intensity-dependent manner [53] (Figure 2). Elevated ghrelin levels following exercise in individuals with obesity may represent a compensatory mechanism to stimulate appetite and counteract weight loss [54]. Ghrelin administration increases the frequency of meals to cause weight gain. Acute bouts of exercise modulate blood levels of ghrelin, with some studies reporting that ghrelin release is suppressed during running and resistance exercise [31; 55; 56]. Exercise intensity and duration are the main determinants of ghrelin response to acute exercise [57]. Rope jumping (3 \(\times\) 10 min/5 min interval) and exercise on a cycle ergometer (3 \(\times\) 10 min/5 min interval) reduce ghrelin release [58]. The main mechanism by which ghrelin is reduced by acute exercise may partly be related to its synthesis, where exercise lowers conversion to its active form by modulating ghrelin-O-acyltransferase (GOAT) [59; 60] (an enzyme that catalyzes its post-translational modification by adding a medium-chain fatty acid to its third N-terminal amino acid residue) [61], increased sympathetic output, elevated gastric mucosal ischemia via the redistribution of blood flow from splanchnic circulation to skeletal muscles during exercise [37], and increased growth hormone (GH) secretion, which exerts negative feedback on ghrelin production [62] (Figure 2). Exercise intensity is another factor that antagonizes ghrelin release. High-intensity exercises increase circulatory levels of lactate (Figure 2), which in turn suppress ghrelin  
Figure 1: Changes in some appetite-regulating hormones, hepatokines, adipokines, and neurotrophic factors in obesity. CCK, cholecystkinin; BDNF, brain-derived neurotrophic factor; GDF14, growth differentiation factor 15; GLP-1, glucagon-like peptide 1; IL-6, interleukin-6; PYY, peptide YY. Figure 2: Biological pathways by which exercise suppresses appetite.