**2. Growth hormone**

GH is secreted at the anterior pituitary gland in a pulsatile manner and is primarily regulated by hypothalamic neuropeptides GH-releasing hormone and somatostatin, which stimulate and inhibit GH secretion, respectively [21]. It is known that resistance exercise (RE) is considered the most effective potent and physiological stimulus for GH release [22, 23], but little about how RE alters somatotroph content and function. Importantly, Rudman et al. [24] verified that when GH was administered to older healthy male, there were substantial decrease in AT mass, and significant increase in lean body mass. After that, studies have shown that GH therapy can improve VAT, circulating lipid levels, and insulin resistance in individuals with obesity and/or diabetes [15, 25]. In addition, it was observed the potential utility of GH therapy for the amelioration of age-related declines in metabolic function and body composition. GH is a potent anabolic hormone that affects multiple systems within the body and plays a significant role in lipid metabolism at various sites, such as liver, skeletal muscle, and AT [26]. Meanwhile, side effects of GH therapy such as an increased likelihood of soft tissue edema, joint pain, carpal tunnel syndrome, gynecomastia, hypertension, and diabetes have been reported [27, 28]. Considering these findings, exogenous GH therapy would became typically reserved for individuals with GH deficiencies resulting from hypothalamic/pituitary disease [29]. Despite this, there has since been increasing interest in identifying therapies, including lifestyle interventions, that increase physiologic GH release and action.

Considering the obesity, the somatotropic axis, that is a primary regulator of the metabolism, has particular relevance. The somatotropic axis consists of GH and insulin-like growth factors (IGF-I and IGF-II), and related to carrier proteins and receptors, which are further regulated by nutritional status and hormones such as ghrelin and insulin [30, 31]. During periods of fasting or stress, GH promotes the use of lipids as the primary fuel source in order to preserve carbohydrates and protein stores. In the liver, lipid uptake and production are increased through the phosphorylation of sterol regulatory element-binding proteins and by increased lipoprotein lipase (LPL) expression. In addition, GH also indirectly would increase the fatty acid oxidation and, additionally, would activate the adenosine monophosphate-activated protein kinase pathway [21].

GH is a powerful regulator of lipid metabolism, but its effect depends on the target. GH has lipogenic effects within the liver, however, the opposite occurs in AT, particularly VAT, where GH elicits lipolytic effects due to the suppression of LPL activity [17]. During exercise or fasting, GH stimulates the release of free fatty acids (FFAs) in the circulation to be delivered to various organs, including myocytes. In this case, FFAs may be repackaged as triglycerides or undergo β-oxidation in the mitochondria. While it is recognized that GH also elicits various effects on glucose and protein metabolism, exercise induced alterations in physiologic GH appear to primarily affect the AT lipolysis [32, 33].

Increased ectopic fat, such as VAT and intrahepatic triglyceride, contributes to insulin resistance and may affect the feedback control system of the somatotropic axis, resulting in a cascade of metabolic impairments [31].
