Intramyocellular lipid accumulation is associated with permanent relocation ex vivo and in vitro of fatty acid translocase (FAT)/CD36 in obese patients

被引：93

作者：

Aguer, C. ^{[1
,2
]}

Mercier, J. ^{[1
,2
,3
]}

Man, C. Yong Wai ^{[1
,2
]}

Metz, L. ^{[1
,2
]}

Bordenave, S. ^{[1
,2
]}

Lambert, K. ^{[1
,2
]}

Jean, E. ^{[1
,2
]}

Lantier, L. ^{[4
,5
]}

Bounoua, L. ^{[6
]}

Brun, J. F. ^{[1
,2
,3
]}

de Mauverger, E. Raynaud ^{[1
,2
,3
]}

Andreelli, F. ^{[4
,5
,7
]}

Foretz, M. ^{[4
,5
]}

Kitzmann, M. ^{[1
,2
]}

机构：

[1] Hop A de Villeneuve, INSERM, Muscle & Pathol ER125, F-34295 Montpellier, France

[2] Univ Montpellier I, Muscle & Pathol EA4202, Montpellier, France

[3] Hop Lapeyronie, CHU Montpellier, CERAMM, Montpellier, France

[4] Univ Paris 05, CNRS, Inst Cochin, UMR8104, Paris, France

[5] INSERM, U567, Paris, France

[6] Univ Aix Marseille 1, CNRS, LPC, UMR 6146, Marseille, France

[7] CHU Bichat Claude Bernard, AP HP, Serv Diabetol, Paris, France

来源：

DIABETOLOGIA | 2010年 / 53卷 / 06期

关键词：

Human myotubes; Lipid; Obesity; Skeletal muscle; Type; 2; diabetes; HUMAN SKELETAL-MUSCLE; TYPE-2 DIABETIC SUBJECTS; BLOOD LACTATE REMOVAL; OXIDATIVE CAPACITY; TRIACYLGLYCEROL ACCUMULATION; MITOCHONDRIAL RESPIRATION; SUPRAMAXIMAL EXERCISE; INSULIN-RESISTANCE; FATIGUE INDEXES; TRANSPORT;

D O I：

10.1007/s00125-010-1708-x

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Intramyocellular lipids (IMCL) accumulation is a classical feature of metabolic diseases. We hypothesised that IMCL accumulate mainly as a consequence of increased adiposity and independently of type 2 diabetes. To test this, we examined IMCL accumulation in two different models and four different populations of participants: muscle biopsies and primary human muscle cells derived from non-obese and obese participants with or without type 2 diabetes. The mechanism regulating IMCL accumulation was also studied. Muscle biopsies were obtained from ten non-obese and seven obese participants without type 2 diabetes, and from eight non-obese and eight obese type 2 diabetic patients. Mitochondrial respiration, citrate synthase activity and both AMP-activated protein kinase and acetyl-CoA carboxylase phosphorylation were measured in muscle tissue. Lipid accumulation in muscle and primary myotubes was estimated by Oil Red O staining and fatty acid translocase (FAT)/CD36 localisation by immunofluorescence. Obesity and type 2 diabetes are independently characterised by skeletal muscle IMCL accumulation and permanent FAT/CD36 relocation. Mitochondrial function is not reduced in type 2 diabetes. IMCL accumulation was independent of type 2 diabetes in cultured myotubes and was correlated with obesity markers of the donor. In obese participants, membrane relocation of FAT/CD36 is a determinant of IMCL accumulation. In skeletal muscle, mitochondrial function is normal in type 2 diabetes, while IMCL accumulation is dependent upon obesity or type 2 diabetes and is related to sarcolemmal FAT/CD36 relocation. In cultured myotubes, IMCL content and FAT/CD36 relocation are independent of type 2 diabetes, suggesting that distinct factors in obesity and type 2 diabetes contribute to permanent FAT/CD36 relocation ex vivo.

引用

页码：1151 / 1163

页数：13

共 48 条

[1] Lipid content and response to insulin are not invariably linked in human muscle cells [J].