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

• Published in: PloS one 2013-03, Vol.8 (3), p.e55632-e55632
• Main Authors: Lindegaard, Birgitte, Hvid, Thine, Grøndahl, Thomas, Frosig, Christian, Gerstoft, Jan, Hojman, Pernille, Pedersen, Bente Klarlund
• Format: Article
• Language: English
• Subjects: Adult; Anticoagulants; Biology; Body fat; Case-Control Studies; Cholesterol; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Drug therapy; Fasting; Female; Fibroblast growth factors; Fibroblast Growth Factors - blood; Fibroblast Growth Factors - genetics; Fibroblast Growth Factors - metabolism; Fibroblasts; Gene expression; Glucose; Glucose metabolism; Glucose tolerance; Glucose tolerance test; Glycogen; Glycogen synthase; Glycogen synthesis; Growth factors; Health aspects; Hip; HIV; HIV Infections - blood; HIV Infections - genetics; HIV Infections - metabolism; HIV patients; Human immunodeficiency virus; Humans; Infection; Infectious diseases; Inflammation; Insulin; Insulin resistance; Insulin Resistance - genetics; Insulin Resistance - physiology; Lipid metabolism; Lipids; Lipodystrophy; Lipodystrophy - blood; Lipodystrophy - genetics; Lipodystrophy - metabolism; Male; Medicine; Metabolism; Middle Aged; Mitochondrial DNA; Muscle, Skeletal - metabolism; Muscles; Musculoskeletal system; Patients; Physiological aspects; Physiology; RNA; Rodents; Skeletal muscle; Studies; Triglycerides; Type 2 diabetes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0055632

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. 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. 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. 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.