Accumulation of advanced glycation end-products and activation of the SCAP/SREBP Lipogenetic pathway occur in diet-induced obese mouse skeletal muscle.
Aim of this study was to investigate whether advanced glycation end-products (AGEs) accumulate in skeletal myofibers of two different animal models of diabesity and whether this accumulation could be associated to myosteatosis. Male C57Bl/6j mice and leptin-deficient ob/ob mice were divided into three groups and underwent 15 weeks of dietary manipulation: standard diet-fed C57 group (C57, n = 10), high-fat high-sugar diet-fed C57 group (HFHS, n = 10), and standard diet-fed ob/ob group (OB/OB, n = 8). HFHS mice and OB/OB mice developed glycometabolic abnormalities in association with decreased mass of the gastrocnemius muscle, fast-to-slow transition of muscle fibers, and lipid accumulation (that occurred preferentially in slow compared to fast fibers). Moreover, we found in muscle fibers of HFHS and OB/OB mice accumulation of AGEs that was preferential for the lipid-accumulating cells, increased expression of the lipogenic pathway SCAP/SREBP, and co-localisation between AGEs and SCAP-(hyper)expressing cells (suggestive for SCAP glycosylation). The increased expression of the SCAP/SREBP lipogenic pathway in muscle fibers is a possible mechanism underlying lipid accumulation and linking myosteatosis to muscle fiber atrophy and fast-to-slow transition that occur in response to diabesity.
Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
Raffaella
R
Mastrocola
Department of Drug Science and Technology, University of Turin, Turin, Italy.
Massimo
M
Collino
Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
Debora
D
Nigro
Department of Drug Science and Technology, University of Turin, Turin, Italy.
Fausto
F
Chiazza
Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Giuseppe
G
D'Antona
Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
Manuela
M
Aragno
Division of Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, Turin, Italy.
Marco A
MA
Minetto
D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D017127:Glycation End Products, Advanced / Q000097:blood*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D050155:Lipogenesis; D008565:Membrane Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism; D009765:Obesity / Q000097:blood* / Q000209:etiology; D051779:Sterol Regulatory Element Binding Proteins / Q000378:metabolism
D017127:Glycation End Products, Advanced; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C102196:SREBP cleavage-activating protein; D051779:Sterol Regulatory Element Binding Proteins; D018995:Myosin Heavy Chains