# Exercise Suppresses Appetite in Obesity: A Biochemical, Metabolic, and Molecular Approach
## 7 Exercise, Mental Stress, and Appetite  
Reducing mental stress is another mechanism through which exercise can suppress appetite (Figure 6). Mental stress is associated with the hyperactivation of both the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis (HPA), which in turn increases the production of catecholamines and cortisol [539; 540]. Cortisol causes hyperinsulinemia [541; 542] by inhibiting glucose transporter type 4 (GLUT4) recruitment to the cell membrane and reducing IRS-1 levels [543]. Hyperinsulinemia increases body fat mass by inhibiting fatty acid oxidation, and hypercortisolemia also leads to leptin resistance and increased NPY levels [544; 545; 546]. Insulin, cortisol, and NPY are critical instigators of appetite and increased food consumption [547; 548; 549]. Increased food intake reduces stress by impacting the corticolimbic area of the brain, a region related to sensing pleasure and stress [550; 551]. There is an inverse correlation between exercise and stress levels [552]. A high level of physical fitness reduces psychological stressors [539; 553] and attenuates sympathetic responses to stress [554] (Figure 6). Lower depressive states and reduced rates of urine cortisol (as a parameter of HPA activity) and lower epinephrine levels (as an indicator of sympathetic system activity) occur after 8 of weeks regular exercise in females with mild to moderate depression [555]. Activation of the HPA causes cortisol release by the pituitary gland, which secretes adrenocortic hormones, which in turn stimulate cortisol secretion from the adrenal cortex. Lower cortisol concentrations after chronic exercise may partly refer to the attenuated rate of perceived exertion for performing a given exercise [556]. In addition, the increased secretion of neurotransmitters such as serotonin and dopamine after exercise training triggers the secretion of endorphins, which are associated with euphoria and may lower psychological stress [557; 558] (Figure 6). In summary, reduced levels of stress hormones and increases in pleasure hormones following exercise are associated with reduced psychological stress, which in turn suppresses appetite. to the activation of \(\beta\)-adrenergic receptors. Increased body temperature triggered by BAT activation leads reduced serum ghrelin concentrations that can suppress appetite [563; 564; 565; 566; 567] (Figure 6). The specific mechanisms by which body temperature affects hormone secretion and signaling are unclear, but recent studies indicate that the BAT-stimulated regulation of food intake is related to secretion, a satiety hormone [568; 569]. Secretin binds to its receptors on BAT and activates BAT thermogenesis to then activate POMC neurons in the media-basal hypothalamus by afferent sensory neurons innervating BAT [569; 570; 571; 572], leading to quenching brain reward-related responses to food cues [573; 574] (Figure 6). The core body temperature is increased after exposure to a high-temperature environment, prolonged exercise, and in pathological conditions such as febrile diseases. These conditions can suppress appetite instantly, after several hours, or days after exposure. The activation of POMC neurons in response to warm temperatures is mediated by temperature-sensitive cation channels of transient receptor potential vanilloid 1 (TRPV1) [575] (Figure 6). TRPV1 channels belong to the transient receptor potential (TRP) cation channel family and consist of four subunits (TRPV1-4). These channels transduce information on core body and ambient temperatures to the ARC region of the hypothalamus that controls the core body temperature. Both TRPV1 and TRPV2 ion channels transduce noxious temperatures such that TRPV1 channels are sensitive to temperatures of up to 42 \({}^{\circ}\)C [575] and TRPV2 channels are sensitive to temperatures higher than 52 \({}^{\circ}\)C [576]. Additionally, the sensitivity of the TRPV3 and TRPV4 channels are in the innocuous ranges of 32-39 \({}^{\circ}\)C [577] and 27-35 \({}^{\circ}\)C [578], respectively.