title: Myotubes from severely obese type 2 diabetic subjects accumulate less lipids and show higher lipolytic rate than myotubes from severely obese non-diabetic subjects.
abstract: About 80% of patients with type 2 diabetes are classified as overweight. However, only about 1/3 of severely obese subjects have type 2 diabetes. This indicates that several severely obese individuals may possess certain characteristics that protect them against type 2 diabetes. We therefore hypothesized that this apparent paradox could be related to fundamental differences in skeletal muscle lipid handling. Energy metabolism and metabolic flexibility were examined in human myotubes derived from severely obese subjects without (BMI 44±7 kg/m2) and with type 2 diabetes (BMI 43±6 kg/m2). Lower insulin sensitivity was observed in myotubes from severely obese subjects with type 2 diabetes. Lipolysis rate was higher, and oleic acid accumulation, triacylglycerol content, and fatty acid adaptability were lower in myotubes from severely obese subjects with type 2 diabetes compared to severely obese non-diabetic subjects. There were no differences in lipid distribution and mRNA and protein expression of the lipases HSL and ATGL, the lipase cofactor CGI-58, or the lipid droplet proteins PLIN2 and PLIN3. Glucose and oleic acid oxidation were also similar in cells from the two groups. In conclusion, myotubes established from severely obese donors with established type 2 diabetes had lower ability for lipid accumulation and higher lipolysis rate than myotubes from severely obese donors without diabetes. This indicates that a difference in intramyocellular lipid turnover might be fundamental in evolving type 2 diabetes.
authors: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway.
authors: Siril S
authors: SS
authors: Bakke
authors: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway.
authors: Yuan Z
authors: YZ
authors: Feng
authors: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway.
authors: Natasa
authors: N
authors: Nikolić
authors: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway.
authors: Eili T
authors: ET
authors: Kase
authors: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, University of Toulouse, Toulouse, France.
authors: Cedric
authors: C
authors: Moro
authors: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway.
authors: Camilla
authors: C
authors: Stensrud
authors: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway.
authors: Lisbeth
authors: L
authors: Damlien
authors: Faculty of Health, Oslo and Akershus University College of Applied Sciences, Oslo, Norway.
authors: Marianne O
authors: MO
authors: Ludahl
authors: The Morbid Obesity Center, Vestfold Hospital Trust, Tønsberg, Norway.
authors: Rune
authors: R
authors: Sandbu
authors: The Morbid Obesity Center, Vestfold Hospital Trust, Tønsberg, Norway.
authors: Brita Marie
authors: BM
authors: Solheim
authors: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway.
authors: Arild C
authors: AC
authors: Rustan
authors: The Morbid Obesity Center, Vestfold Hospital Trust, Tønsberg, Norway; Department of Pharmacology, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway.
authors: Jøran
authors: J
authors: Hjelmesæth
authors: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway; Department of Pharmacology, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway.
authors: G Hege
authors: GH
authors: Thoresen
authors: Faculty of Health, Oslo and Akershus University College of Applied Sciences, Oslo, Norway.
authors: Vigdis
authors: V
authors: Aas
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology*; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D008049:Lipase / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology*; D008066:Lipolysis; D008565:Membrane Proteins / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism / Q000473:pathology*; D019301:Oleic Acid / Q000378:metabolism; D010084:Oxidation-Reduction; D000070780:Perilipin-2; D000070796:Perilipin-3; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012720:Severity of Illness Index; D014280:Triglycerides / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D008565:Membrane Proteins; C000602982:PLIN2 protein, human; C038196:PLIN3 protein, human; D000070780:Perilipin-2; D000070796:Perilipin-3; D014280:Triglycerides; D033921:Vesicular Transport Proteins; D019301:Oleic Acid; D051057:Proto-Oncogene Proteins c-akt; D008049:Lipase