Irisin levels in LMNA-associated partial lipodystrophies - 24/01/19

Doi : 10.1016/j.diabet.2018.08.003

F. Bensmaïne ^a, K. Benomar ^a, S. Espiard ^a, C. Vahe ^a, K. Le Mapihan ^a, G. Lion ^b, M. Lemdani ^c, E. Chazard ^c, O. Ernst ^d, C. Vigouroux ^e,^f,^g, P. Pigny ^h,^{^{1
The 2 last authors have equally contributed.}}, M.-C. Vantyghem ^a,^g,^i,^{^{1
The 2 last authors have equally contributed.},}^⁎
^a Department of endocrinology and metabolism, Lille university hospital, 59037 Lille, France
^b Department of nuclear medicine, Lille university hospital, 59037 Lille, France
^c Department of public health, university Lille EA 2694, 59000 Lille, France
^d Department of radiology, Lille university hospital, 59037 Lille France
^e Inserm UMR_S938, departments of endocrinology and molecular biology and genetics, Saint-Antoine hospital, Saint-Antoine research centre, Sorbonne université, Assistance publique-Hôpitaux de Paris (AP–HP), 75012 Paris, France
^f Institute of cardiometabolism and nutrition (ICAN), 75013 Paris, France
^g National reference centre of rare diseases of insulin secretion and of insulin sensitivity, hospital Saint-Antoine, 75012 Paris, France
^h Department of biology, Lille university hospital, 59037 Lille France
ⁱ Inserm U1190, European genomic institute for diabetes, 59000 Lille, France

^⁎Corresponding author: Endocrinology and metabolism department, C.-Huriez hospital, Lille university, 1, rue Polonovski, 59037 Lille cedex, France.Endocrinology and metabolism departmentC.-Huriez hospitalLille university1, rue PolonovskiLille cedex59037France

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Abstract

Aim

The adipo-myokine irisin regulates energy expenditure and fat metabolism. LMNA-associated familial partial lipodystrophy (FPLD2) comprises insulin resistance, muscle hypertrophy and lipoatrophy. The aim of this study was to investigate whether irisin could be a biomarker of FPLD2.

Patients and methods

This case control study included 19 FPLD2 subjects, 13 obese non-diabetic (OND) patients and 19 healthy controls (HC) of normal weight (median BMI: 26, 39 and 22 kg/m², respectively). Serum irisin and leptin levels, body composition (DXA/MRI) and metabolic/inflammatory parameters were compared in these three groups.

Results

BMI and MRI intra-abdominal fat significantly differed among these three groups, whereas DXA total fat mass and leptin levels were higher in the OND group, but did not differ between HC and FPLD2. Lipodystrophy patients had higher intra-abdominal/total abdominal fat ratios than the other two groups. Irisin levels were higher in FPLD2 and OND patients than in HC (medians: 944, 934 and 804 ng/mL, respectively). However, irisin/leptin ratios and lean body mass percentages were strikingly higher, and lean mass indices lower, in FPLD2 and HC than in the OND (median irisin/leptin ratios: 137, 166 and 21, respectively). In the entire study group, irisin levels positively correlated with BMI, lean body mass and index, intra-abdominal/total abdominal fat ratio, triglyceride, cholesterol, insulin, glucose and HbA_1c levels. Also, intra-abdominal/total abdominal fat ratio and lean body mass better differentiated the three groups only in female patients.

Conclusion

Circulating irisin is similarly increased in FPLD2 and OND patients, who are characterized by higher lean body mass regardless of their clearly different fat mass. However, irisin/leptin ratios, strikingly higher in FPLD2 than in OND patients, could help to make the diagnosis and prompt genetic testing in clinically atypical cases.

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Abbreviations : BMI, DXA, FBG, FPLD2, HbA_1c, HC, OND

Keywords : Fat mass, Irisin, Lamin A, Lean mass, Leptin, Lipodystrophy