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ATP‐BINDING CASSETTE TRANSPORTER ABCA1 IS DECREASED IN SKELETAL MUSCLE FROM INSULIN RESISTANT MICE
Author(s) -
Llanos Paola,
Sanchéz Pablo,
CerdaKohler Hugo,
AriasCalderón Manuel,
DiazVegas Alexis,
Campos Cristián,
ContrerasFerrat Ariel,
Hidalgo Cecilia,
Jaimovich Enrique
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.701.2
Subject(s) - glut4 , abca1 , endocrinology , medicine , glucose transporter , skeletal muscle , insulin resistance , insulin , glucose uptake , adipose tissue , biology , cholesterol , chemistry , transporter , biochemistry , gene
Insulin resistance (IR) is associated with obesity, metabolic syndrome and type 2 diabetes. Skeletal muscle is the main source of GLUT4‐mediated glucose transport in animals. Most GLUT4‐mediated glucose transport occurs in the transverse tubules (TT), a specialized cholesterol‐enriched plasma membrane system of skeletal muscle. In IR, GLUT4 translocation to the TT membrane is defective. Interestingly, we found that cholesterol levels in TT from skeletal muscle are higher in IR mice. We have centered our efforts in understanding the role of cholesterol accumulation in TT in muscle and its relation to IR. We have shown that the cholesterol‐lowering agent methyl‐β‐cyclodextrin promotes glucose uptake in adult muscle fibers and reduces insulin resistance in obese mice. Recent reports indicate that ATP‐binding cassette transporter ABCA1 (ABCA1), a transporter that mediates cellular cholesterol efflux, has a role in regulating lipid content, glucose tolerance and insulin sensitivity in adipose tissue. In skeletal muscle, however, a direct demonstration of the expression for ABCA1 during IR is lacking. MATERIAL AND METHODS Male C57BL/6J mice were fed with normal (NCD) or high fat diet (HFD) for 8‐weeks. qPCR, immunohistochemistry and immunocitochemistry were performed. RESULTS Both, relative mRNA level and protein content of ABCA1 were decreased in muscle homogenates and isolated triads from HFD‐fed mice compared to NCD‐fed mice. In addition, ABCA1 decreased in transversal cross section of whole muscle and isolated fibers from HFD‐fed mice. DISCUSSION The results obtained will help us to define if changes in ABCA1 expression/function contribute to the anomalous cholesterol accumulation displayed by skeletal muscle TT membranes in IR condition. ( pllanos@odontologia.uchile.cl ) Support or Funding Information FIOUCH‐ENLACE 001/2015 and FONDECYT 1151293 & 11150243