RT Journal Article
SR Electronic
T1 Human Adipocytes Induce Inflammation and Atrophy in Muscle Cells During Obesity
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP 3121
OP 3134
DO 10.2337/db14-0796
VO 64
IS 9
A1 Pellegrinelli, Vanessa
A1 Rouault, Christine
A1 Rodriguez-Cuenca, Sergio
A1 Albert, Victorine
A1 Edom-Vovard, Frédérique
A1 Vidal-Puig, Antonio
A1 Clément, Karine
A1 Butler-Browne, Gillian S.
A1 Lacasa, Danièle
YR 2015
UL http://diabetes.diabetesjournals.org/content/64/9/3121.abstract
AB Inflammation and lipid accumulation are hallmarks of muscular pathologies resulting from metabolic diseases such as obesity and type 2 diabetes. During obesity, the hypertrophy of visceral adipose tissue (VAT) contributes to muscle dysfunction, particularly through the dysregulated production of adipokines. We have investigated the cross talk between human adipocytes and skeletal muscle cells to identify mechanisms linking adiposity and muscular dysfunctions. First, we demonstrated that the secretome of obese adipocytes decreased the expression of contractile proteins in myotubes, consequently inducing atrophy. Using a three-dimensional coculture of human myotubes and VAT adipocytes, we showed the decreased expression of genes corresponding to skeletal muscle contractility complex and myogenesis. We demonstrated an increased secretion by cocultured cells of cytokines and chemokines with interleukin (IL)-6 and IL-1β as key contributors. Moreover, we gathered evidence showing that obese subcutaneous adipocytes were less potent than VAT adipocytes in inducing these myotube dysfunctions. Interestingly, the atrophy induced by visceral adipocytes was corrected by IGF-II/insulin growth factor binding protein-5. Finally, we observed that the skeletal muscle of obese mice displayed decreased expression of muscular markers in correlation with VAT hypertrophy and abnormal distribution of the muscle fiber size. In summary, we show the negative impact of obese adipocytes on muscle phenotype, which could contribute to muscle wasting associated with metabolic disorders.