Expression of fibroblast growth factor-21 in muscle is associated with lipodystrophy, insulin resistance and lipid disturbances in patients with HIV.

Abstract

BACKGROUND:

Fibroblast growth factor (FGF)-21 is a novel regulator of glucose and lipid metabolism. Recently, increased FGF-21 mRNA expression in muscle was found in patients with type 2 diabetes, but the role for FGF-21 in muscle is not well understood. Patients with HIV-infection and lipodystrophy are characterised by various degree of lipid-driven insulin resistance. We hypothesized that muscle FGF-21 mRNA would be altered in HIV patients with lipodystrophy.

DESIGN:

Twenty-five HIV-infected men with lipodystrophy (LD) and 15 age-matched healthy controls, received an oral glucose tolerance test and a euglycemic-hyperinsulinemic clamp (50 mU/m2/min) combined with 6,6-H2 glucose infusion. Muscle biopsies were obtained and FGF-21 mRNA and glycogen synthase (GS) activity were measured.

RESULTS:

Subjects with HIV were insulin resistant compared with non-HIV subjects. Compared to controls, HIV subjects demonstrated a twofold increase of plasma FGF-21 from 70.4±56.8 pg/ml vs 109.1±71.8 pg/ml, respectively (p = 0.04) and an eight-fold increase in muscular FGF-21 mRNA expression (p = 0.001). Muscle FGF-21 mRNA correlated inversely with the rate of disappearance of glucose during insulin clamp (r = -0.54, p = 0.0009), and the GS fractional velocity in muscle (r = -0.39, p = 0.03), and directly with fasting insulin (r = 0.50, p = 0.0022), HOMA-IR (r = 0.47, p = 0.004), triglycerides (r = 0.60. P = 0.0001), waist-to-hip ratio (r = 0.51, p = 0.0001) and limb fat mass (-0.46, p = 0.004), but not to plasma FGF-21.

CONCLUSION:

FGF-21 mRNA is increased in skeletal muscle in HIV patients and correlates to whole-body (primarily reflecting muscle) insulin resistance, but not to plasma FGF-21. Those findings add to the evidence that FGF-21 is a myokine and may suggest that muscle FGF-21 is working in a local manner.

• Authors: Birgitte Lindegaard, Thine Hvid, Thomas Grøndahl, Christian Frosig, Jan Gerstoft, Pernille Hojman, Bente Klarlund Pedersen
• Journal: PloS one (PLoS One) Vol. 8 Issue 3 Pg. e55632 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23533568 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• fibroblast growth factor 21
• Fibroblast Growth Factors

Topics

• Adult
• Case-Control Studies
• Female
• Fibroblast Growth Factors (blood, genetics, metabolism)
• HIV Infections (blood, genetics, metabolism)
• Humans
• Insulin Resistance (genetics, physiology)
• Lipodystrophy (blood, genetics, metabolism)
• Male
• Middle Aged
• Muscle, Skeletal (metabolism)