Expression of fibroblast growth factor-21 in muscle is associated with lipodystrophy, insulin resistance and lipid disturbances in patients with HIV.
PLoS One
; 8(3): e55632, 2013.
Article
in En
| MEDLINE
| ID: mdl-23533568
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 (pâ=â0.04) and an eight-fold increase in muscular FGF-21 mRNA expression (pâ=â0.001). Muscle FGF-21 mRNA correlated inversely with the rate of disappearance of glucose during insulin clamp (râ=â-0.54, pâ=â0.0009), and the GS fractional velocity in muscle (râ=â-0.39, pâ=â0.03), and directly with fasting insulin (râ=â0.50, pâ=â0.0022), HOMA-IR (râ=â0.47, pâ=â0.004), triglycerides (râ=â0.60. Pâ=â0.0001), waist-to-hip ratio (râ=â0.51, pâ=â0.0001) and limb fat mass (-0.46, pâ=â0.004), 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Insulin Resistance
/
HIV Infections
/
Muscle, Skeletal
/
Fibroblast Growth Factors
/
Lipodystrophy
Type of study:
Observational_studies
/
Risk_factors_studies
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
PLoS One
Journal subject:
CIENCIA
/
MEDICINA
Year:
2013
Type:
Article
Affiliation country:
Denmark