title: The Role of PGC-1α in the Development of Insulin Resistance in Skeletal Muscle - Revisited.
abstract: Currently, obesity is a predominant medical condition and an important risk factor for the development of several diseases, including type 2 diabetes mellitus. Importantly, most research has indicated lipid-induced insulin resistance in skeletal muscles is a key link between the aforementioned pathological conditions. PGC-1α is a prominent regulator of myocellular energy metabolism orchestrating gene transcription programming in response to numerous environmental stimuli. Moreover, it is widely acknowledged that mitochondrial metabolism (primary metabolic target of PGC-1α) disturbances are widely acknowledged contributors to type 2 diabetes development. Therefore, it seems surprising that the exact physiological contribution of PGC-1α in the development of insulin resistance in skeletal muscle remains poorly understood. This review aims to reconcile these allegedly different findings by looking for a common denominator in the role(s) of PGC-1α in respect to lipid-induced insulin resistance in skeletal muscle. Our scrutiny of the literature indicates that interventions at the level of PGC-1α may exert beneficial effects on myocytes in respect to lipid-induced insulin resistance. The latter takes place as a result of a positive net energy balance (fatty acids oxidation surpassing their accumulation rate). Moreover, the aforementioned effects may not necessarily be limited to physically active states. They seem to occur, however, only within a physiologically observed range in muscle cells (approximately 1-fold changes in PGC-1α protein expression).
authors.affiliation: Department of Physiology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Bartlomiej
authors.initials: B
authors.lastname: Łukaszuk
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kurek
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Mikłosz
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Żendzian-Piotrowska
authors.forename: Adrian
authors.initials: A
authors.lastname: Chabowski
mesh_terms: D000818:Animals; D006801:Humans; D007333:Insulin Resistance; D008055:Lipids / Q000737:chemistry; D018482:Muscle, Skeletal / Q000503:physiopathology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D008055:Lipids; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors