# Exercise Suppresses Appetite in Obesity: A Biochemical, Metabolic, and Molecular Approach
## 2 Exercise and Appetite-Regulatory Hormones
AgRP, agouti-related protein; AMPK, adenosine monophosphate-activated protein kinase; BDNF, brain-derived neurotrophic factor; CCK, cholecystkinin; GH, growth hormone; GLP-1, glucagon-like peptide 1; GLP-1R, glucagon-like peptide 1 receptor; GOAT, ghrelin-O-acyltransferase; JAKZ/STAT3, Janus tyrosine kinase 2/signal transducer and activator of transcription 3; NPY, neuropeptide Y; NYPRs, neuropeptide Y receptors; ObRb, leptin receptor; POMC, pro-opiomelancortin; PYY, peptide YY; SNS, sympathetic nervous system; SOCS3, suppressor of cytokine signaling 3.  
production by binding to G-protein-coupled receptor 81 (GPCR81) in gastric cells [63]. Paradoxically, training programs can increase the ghrelin concentration mainly as a result of weight loss [64; 65]. Some studies reported that increased ghrelin levels following long-term training and in individuals with obesity were higher than after short-term training and in individuals with normal body weight [66; 67]. Training programs that caused no changes in body weight failed to increase ghrelin levels [68; 69]. Other studies indicate that acute and chronic exercises lower leptin levels [70; 71; 72], which may partly be ascribed to abated body fat and increased muscle mass (Figure 2). Leptin is mostly synthesized in and released from adipose tissue, and exercise-induced reductions in its concentration induced a compensatory response to increases in appetite [73; 74]. As one of the major signals of energy status, leptin levels impact appetite, satiety, and motivational behaviors (e.g., feeding and foraging behaviors) related to the maintenance of energy reserves. Plasma levels of leptin correlate with energy reserves, particularly triglycerides (TGs) stored in adipose tissue. The brain responds to circulatory leptin, where high leptin levels signify high energy reserves and low leptin levels indicate low energy reserves, allowing the organism to adapt to starvation through a variety of metabolic, endocrine, neurobiochemical, and behavioral changes [75]. Leptin receptors (LEPRs) are expressed by a variety of brain areas related to feeding [76; 77]. There is decreased sensitivity to leptin, or rather, leptin resistance in obesity, resulting in an inability to detect satiety despite high energy stores and high circulating levels of leptin [78]. Leptin resistance in the brain of individuals with obesity has been widely documented and is associated with both impaired intracellular signaling pathways [79; 80; 81; 82; 83] and reduced expression of regulatory proteins, including suppressor of cytokine signaling (SOCS) proteins [84; 85; 86; 87]. The effects of a long-term diet and exercise program (6 months) on plasma leptin concentrations was studied in 21 men and women with obesity. Weight loss decreased plasma leptin concentrations, indicating improved leptin sensitivity (Figure 2). The decrease in plasma leptin concentrations was correlated with reductions in body weight and body fat mass [88]. Although exercise reduces circulatory leptin levels, the improvement in leptin signaling and its sensitivity in the central nervous system offset such reductions. In an investigation by [PERSON] et al. (2013), it was reported that aerobic exercise (1 h/day, 5 days/week, for 12 months), compared with high-intensity exercise, lowered both body weight and leptin levels and promoted hypothalamic leptin sensitivity [89]. Similarly, a reduction in leptin concentration occurred after 5 months of aerobic exercise [90] and 6 months of resistance exercise [70]. The underlying mechanisms of reductions in leptin levels following exercise may be due to increases in growth hormone and testosterone [91; 92] and reduced cortisol levels [93; 94] (Figure 2). A reduction in amplitude in the fluctuation in leptin levels occurs following exercises with a long duration (more than 60 min) that result in an energy imbalance [95; 96]. Thus, there is also a negative correlation between the rate of energy expenditure and circulatory leptin concentration.