Lipodystrophy HIV-related and FGF21: A new marker to follow the progression of lipodystrophy?

Abstract

Recently new evidence about fibroblast growth factor 21 (FGF21) highlights the opportunities to use this molecule in new pharmaceutical formulations to combat type 2 diabetes and metabolic syndrome. It is well known that HIV is per se a condition of insulin resistance and in particular the patient with HIV-related lipodystrophy has a condition strictly related to metabolic syndrome. Lipodystrophy is associated with severe metabolic side effects, including dyslipidemia, hepatic insulin resistance, and lipid oxidation impairment. Research carried out showed that FGF21 levels were significantly increased in untreated HIV-1-infected patients and the increase was much marked in HIV-1-infected antiretroviral-treated patients that have developed lipodystrophy and in the patients with greatest metabolic alterations. FGF21 is expressed mainly by the liver, but also by other tissues such as the thymus, adipose tissue, and skeletal muscle. Therefore, many researchers have considered the investigation of possible variations of FGF21 in patients with significant alterations in body composition both in regard to fat mass and lean mass. In the light of the possible interactions between FGF21 and metabolic syndrome, it seems interesting to evaluate the implication of this hormone in patients with HIV-related lipodystrophy who have a severe metabolic picture of insulin resistance with important alterations in body composition.

Tanycytes Regulate Lipid Homeostasis by Sensing Free Fatty Acids and Signaling to Key Hypothalamic Neuronal Populations via FGF21 Secretion

“…The use of lean Fgf21-deleted mice (Fgf21-KO and Fgf21 liver KO) or Fgfr1 WAT KO mice has shown that Fgf21 limits lipotoxicity by reducing circulating FFAs and hepatic FA accumulation (Badman et al, 2007;Fisher et al, 2014;Yang et al, 2012). Recently, it was proposed that Fgf21-dependent improvement in serum FFAs and hepatic steatosis relies on a direct brain Fgf21 signaling (Benedini and Luzi, 2016;Nies et al, 2015). Our study supports this view, as we show that Fgf21 acts centrally to regulate lipid metabolism in scWAT and liver.…”

Activation of brown adipose tissue by a low-protein diet ameliorates hyperglycemia in a diabetic lipodystrophy mouse model

“…In supporting this point of view, previous reports have shown significantly increased plasma FGF21 in lipodystrophy mice and humans as well as diabetic patients 64 , 65 . Furthermore, FGF21 plasma levels have been proposed as a marker for the following lipodystrophy in human immunodeficiency virus (HIV)-positive patients 66 .…”

Non-Alcoholic Fatty Liver Disease in HIV/HBV Patients – a Metabolic Imbalance Aggravated by Antiretroviral Therapy and Perpetuated by the Hepatokine/Adipokine Axis Breakdown

“…The detection of a high FGF21 serum level in these patients was associated with MetS, lipodistrophy, and severe steatosis ( 239 – 241 ). Given the strong correlations between FGF21 and metabolic parameters, FGF21 has been suggested as a possible prognostic marker to monitor HALS and its therapy as well as the ART-associated cardiovascular risk ( 242 ). HIV infected patients also show high serum levels of resistin, an adipokine correlated with IR, lipoatrophy and NAFLD ( 243 ).…”