Testosterone treatment improves metabolic syndrome-induced adipose tissue derangements

Abstract

We recently demonstrated that testosterone dosing ameliorated the metabolic profile and reduced visceral adipose tissue (VAT) in a high-fat diet (HFD)-induced rabbit model of metabolic syndrome (MetS). We studied the effects of HFD and in vivo testosterone dosing on VAT function and the adipogenic capacity of rabbit preadipocytes isolated from VAT of regular diet (RD), HFD, and testosterone-treated HFD rabbits. VAT was studied by immunohistochemistry, western blot, and RT-PCR. Isolated rPADs were exposed to adipocyte differentiating mixture (DIM) to evaluate adipogenic potential. Adipocyte size was significantly increased in HFD VAT compared with RD, indicating adipocyte dysfunction, which was normalized by testosterone dosing. Accordingly, perilipin, an anti-lipolytic protein, was significantly increased in HFD VAT, when compared with other groups. HFD VAT was hypoxic, while testosterone dosing normalized VAT oxygenation. In VAT, androgen receptor expression was positively associated with mRNA expression of GLUT4 (SLC2A4) (insulin-regulated glucose transporter) and STAMP2 (STEAP4) (androgen-dependent gene required for insulin signaling). In testosterone-treated HFD VAT, STAMP2 mRNA was significantly increased when compared with the other groups. Moreover, GLUT4 membrane translocation was significantly reduced in HFD VAT, compared with RD, and increased by testosterone. In DIM-exposed preadipocytes from HFD, triglyceride accumulation, adipocyte-specific genes, insulin-stimulated triglyceride synthesis, glucose uptake, and GLUT4 membrane translocation were reduced compared with preadipocytes from RD and normalized by in vivo testosterone dosing. In conclusion, testosterone dosing in a MetS animal model positively affects VAT functions. This could reflect the ability of testosterone in restoring insulin sensitivity in VAT, thus counteracting metabolic alterations.

Nonalcoholic steatohepatitis as a novel player in metabolic syndrome-induced erectile dysfunction: An experimental study in the rabbit

“…We recently demonstrated that T supplementation in HFD-MetS animals, prevented hypertrophic and dysfunctional expansion of VAT, restoring lipid droplet handling and insulin sensitivity in adipocytes (Maneschi et al, 2012). We now propose this anti-inflammatory effect on the liver as an additional mechanism by which T could improve metabolic control.…”

Effect of testosterone on markers of mitochondrial oxidative phosphorylation and lipid metabolism in muscle of aging men with subnormal bioavailable testosterone

“…This suggests that other peripheral tissues than skeletal muscle may be more responsible for the increase in whole-body lipid oxidation. For example, recent animal studies have demonstrated a positive effect of testosterone on adipocyte dysfunction and differentiation capacity (41). Thus, other tissues including different types of adipose tissue and the In our study, aging men with subnormal bioavailable testosterone below 7.3 nmol/l were included.…”

Nonalcoholic steatohepatitis as a novel player in metabolic syndrome-induced erectile dysfunction: an experimental study in the rabbit

“…Cutoffs for each factor were derived by the mean ± two S.D. of the analyzed parameter, as measured in RD rabbits according to (Maneschi et al, 2012). Positivity for three or more factors identifies MetS.…”

“…The current study addressed this issue by taking advantage of a non-genomic, high fat diet (HFD)-induced, animal model of MetS that closely resembles the human MetS phenotype (Filippi et al, 2009;Vignozzi et al, 2011Vignozzi et al, , 2012aManeschi et al, 2012;Maneschi et al, 2013). This model is characterized by hyperglycaemia, glucose intolerance, hypercholesterolemia, hypertriglyceridemia, hypertension, increased visceral fat mass, hypogonadotropic hypogonadism, lower urinary tract (LUT) abnormalities (Vignozzi et al, 2012a), penile alterations (Filippi et al, 2009;Vignozzi et al, 2011) and NASH .…”

“…The data indicate that MetS-induced NASH plays an active role in the pathogenesis of ED in HFD rabbits, likely via TNFa. We have recently demonstrated that both testosterone (T; Filippi et al, 2009;Maneschi et al, 2012) or obeticholic acid (OCA; Vignozzi et al, 2011;Maneschi et al, 2013) supplementation to HFD rabbits were able to normalize not only several MetS features, including visceral adipose tissue dysfunction and insulin resistance, but also HFD-induced penile alterations, including hypo-responsiveness to acetylcholine (Ach). Hence, here, we tested whether these treatments can ameliorate also HFD-induced liver alterations, as well as TNFa circulating level.…”