Growth hormone stimulates lipolysis in mice but not in adipose tissue or adipocyte culture

Abstract

The inhibitory effect of growth hormone (GH) on adipose tissue growth and the stimulatory effect of GH on lipolysis are well known, but the mechanisms underlying these effects are not completely understood. In this study, we revisited the effects of GH on adipose tissue growth and lipolysis in the lit/lit mouse model. The lit/lit mice are GH deficient because of a mutation in the GH releasing hormone receptor gene. We found that the lit/lit mice had more subcutaneous fat and larger adipocytes than their heterozygous lit/+ littermates and that these differences were partially reversed by 4-week GH injection. We also found that GH injection to the lit/lit mice caused the mature adipose tissue and adipocytes to reduce in size. These results demonstrate that GH inhibits adipose tissue growth at least in part by stimulating lipolysis. To determine the mechanism by which GH stimulates lipolysis, we cultured adipose tissue explants and adipocytes derived from lit/lit mice with GH and/or isoproterenol, an agonist of the beta-adrenergic receptors. These experiments showed that whereas isoproterenol, expectedly, stimulated potent lipolysis, GH, surprisingly, had no effect on basal lipolysis or isoproterenol-induced lipolysis in adipose tissue explants or adipocytes. We also found that both isoproterenol-induced lipolysis and phosphorylation of hormone-sensitive lipase were not different between lit/lit and lit/+ mice. Taken together, these results support the conclusion that GH has lipolytic effect in mice but argue against the notion that GH stimulates lipolysis by directly acting on adipocytes or by enhancing β-adrenergic receptors-mediated lipolysis.

Association of growth hormone deficiency with an increased number of preadipocytes in subcutaneous fat

“…The inhibitory effect of GH on adipose tissue growth has been demonstrated by multiple studies (4,52,53), but the underlying mechanism is not fully understood. In a previous study, we found that the GH-deficient lit/lit mice were growth retarded overall but accumulated more subcutaneous fat compared to the GH-normal lit/+ mice at the same age (39). These phenotypes of the GHdeficient lit/lit mice are consistent with those of GHR-null mice (54) and similar to the body weight and body composition changes in GH-deficient humans (53,55).…”

“…The lit/lit mice carry a mutation that disable the GH releasing hormone receptor (ghrhr) gene, and as such, mice homozygous for the mutation (lit/lit) are deficient in GH and smaller than wild-type or lit/+ mice (37,38). In a previous study, we found that the lit/lit mice had more subcutaneous fat than the lit/+ mice despite being much smaller than the latter (39). In this study, we found that the lit/lit mice accumulated more preadipocytes in subcutaneous fat but that terminal differentiation of preadipocytes from the lit/lit mice into adipocytes was not affected by GH in vitro.…”

The central role of mitochondrial metabolism in hepatic steatosis

“…Thyroid hormones regulate serum levels of cholesterol by stimulating cholesterol biosynthesis through inducing HMGCR, cholesterol export [primarily as lowdensity lipoprotein (LDL) and very LDL (VLDL)], reverse transport from peripheral tissues, hepatic reuptake via LDL receptors (LDLRs), and cholesterol conversion into bile acids in the liver [170,171]. The past and updated reviews are recommended for the direct and indirect effects of thyroid hormone on mitochondria [172][173][174][175][176][177]. The sympathetic nervous system stimulates hepatic gluconeogenesis, whereas the parasympathetic system does not.…”