Back to Search
Start Over
FTO Is Increased in Muscle During Type 2 Diabetes, and Its Overexpression in Myotubes Alters Insulin Signaling, Enhances Lipogenesis and ROS Production, and Induces Mitochondrial Dysfunction
- Source :
- Diabetes, Diabetes, 2010, 60 (1), pp.258-268, Diabetes, American Diabetes Association, 2010, 60 (1), pp.258-268, Diabetes, American Diabetes Association, 2011, 60 (1), pp.258-68. ⟨10.2337/db10-0281⟩, HAL, Diabetes, 2011, 60 (1), pp.258-68. ⟨10.2337/db10-0281⟩
- Publication Year :
- 2010
- Publisher :
- American Diabetes Association, 2010.
-
Abstract
- OBJECTIVE A strong association between genetic variants and obesity was found for the fat mass and obesity-associated gene (FTO). However, few details are known concerning the expression and function of FTO in skeletal muscle of patients with metabolic diseases. RESEARCH DESIGN AND METHODS We investigated basal FTO expression in skeletal muscle from obese nondiabetic subjects and type 1 and type 2 diabetic patients, compared with age-matched control subjects, and its regulation in vivo by insulin, glucose, or rosiglitazone. The function of FTO was further studied in myotubes by overexpression experiments. RESULTS We found a significant increase of FTO mRNA and protein levels in muscle from type 2 diabetic patients, whereas its expression was unchanged in obese or type 1 diabetic patients. Moreover, insulin or glucose infusion during specific clamps did not regulate FTO expression in skeletal muscle from control or type 2 diabetic patients. Interestingly, rosiglitazone treatment improved insulin sensitivity and reduced FTO expression in muscle from type 2 diabetic patients. In myotubes, adenoviral FTO overexpression increased basal protein kinase B phosphorylation, enhanced lipogenesis and oxidative stress, and reduced mitochondrial oxidative function, a cluster of metabolic defects associated with type 2 diabetes. CONCLUSIONS This study demonstrates increased FTO expression in skeletal muscle from type 2 diabetic patients, which can be normalized by thiazolidinedione treatment. Furthermore, in vitro data support a potential implication of FTO in oxidative metabolism, lipogenesis and oxidative stress in muscle, suggesting that it could be involved in the muscle defects that characterize type 2 diabetes.
- Subjects :
- Blood Glucose
Male
MESH: Signal Transduction
Biopsy
[SDV]Life Sciences [q-bio]
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Muscle Fibers, Skeletal
VARIANTS
MESH: Thiazolidinediones
MESH: Biopsy
Adenosine Triphosphate
0302 clinical medicine
MESH: Genetic Vectors
MESH: Adenosine Triphosphate
ADULT OBESITY
Insulin
MESH: Proteins
OXIDATIVE STRESS
ComputingMilieux_MISCELLANEOUS
Oligonucleotide Array Sequence Analysis
GENE-EXPRESSION
MESH: Muscle, Skeletal
0303 health sciences
MESH: Middle Aged
MESH: Muscle Fibers, Skeletal
MESH: Oxidative Stress
biology
Myogenesis
MESH: Mitochondria, Muscle
MESH: Reactive Oxygen Species
HUMANS
Middle Aged
HUMAN SKELETAL-MUSCLE
MESH: Gene Expression Regulation
ADIPOSE-TISSUE
FAT MASS
medicine.anatomical_structure
Alpha-Ketoglutarate-Dependent Dioxygenase FTO
Lipogenesis
MESH: Hemoglobin A, Glycosylated
Female
MESH: Diabetes Mellitus, Type 1
Rosiglitazone
Signal Transduction
MESH: Diabetes Mellitus, Type 2
medicine.drug
medicine.medical_specialty
Genetic Vectors
030209 endocrinology & metabolism
MESH: Insulin
Pathophysiology
03 medical and health sciences
MESH: RNA
MESH: Hypoglycemic Agents
Internal medicine
Diabetes mellitus
Internal Medicine
medicine
Hypoglycemic Agents
Muscle, Skeletal
030304 developmental biology
Glycated Hemoglobin
MESH: Humans
Proteins
nutritional and metabolic diseases
Skeletal muscle
medicine.disease
MESH: Male
Mitochondria, Muscle
[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition
Insulin receptor
Diabetes Mellitus, Type 1
Endocrinology
Diabetes Mellitus, Type 2
Gene Expression Regulation
CELLS
MESH: Oligonucleotide Array Sequence Analysis
MESH: Blood Glucose
biology.protein
RNA
Thiazolidinediones
Reactive Oxygen Species
MESH: Female
[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
RESISTANCE
Subjects
Details
- ISSN :
- 1939327X and 00121797
- Volume :
- 60
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....783e228054e21dfb5d1ea6b2c4dfbe8b