Development of insulin resistance in mice lacking PGC-1α in adipose tissues

Abstract

Reduced peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) expression and mitochondrial dysfunction in adipose tissue have been associated with obesity and insulin resistance. Whether this association is causally involved in the development of insulin resistance or is only a consequence of this condition has not been clearly determined. Here we studied the effects of adipose-specific deficiency of PGC-1α on systemic glucose homeostasis. Loss of PGC-1α in white fat resulted in reduced expression of the thermogenic and mitochondrial genes in mice housed at ambient temperature, whereas gene expression patterns in brown fat were not altered. When challenged with a high-fat diet, insulin resistance was observed in the mutant mice, characterized by reduced suppression of hepatic glucose output. Resistance to insulin was also associated with an increase in circulating lipids, along with a decrease in the expression of genes regulating lipid metabolism and fatty acid uptake in adipose tissues. Taken together, these data demonstrate a critical role for adipose PGC-1α in the regulation of glucose homeostasis and a potentially causal involvement in the development of insulin resistance.glucose metabolism | mitochondrial gene expression | thermogenesis | cold exposure | type 2 diabetes

Continuous cold exposure induces an anti-inflammatory response in mesenteric adipose tissue associated with catecholamine production and thermogenin expression in rats

“…Th ese changes might most likely result in the stimulation of UCP-1 expression (Figure 2). Similarly, we also found a cold-induced increase in the expression of PGC-1α, which is the central regulator in the expression of UCP-1 and other thermogenic genes in both the brown and beige fat cells (Lin et al 2004;Kleiner et al 2012).…”

Increased FNDC5 is associated with insulin resistance in high fat-fed mice

“…2012), FNDC5/irisin has also been identified as an adipokine, with increased release stimulated by atypical metabolic disturbances such as obesity and insulin resistance (Kleiner et al. 2012; Roca‐Rivada et al. 2013; Stengel et al.…”

Role of forkhead box protein A3 in age-associated metabolic decline

“…with glucose in saline solution (2 g/kg). Plasma glucose levels were measured in tail blood samples obtained before and at 15,30,60,90, and 120 min after insulin or glucose injections, using the AlphaTrak Blood Glucose Monitoring System (Abbott). Hyperinsulinemiceuglycemic clamp studies were performed as described previously (40).…”

“…Peroxisome proliferator-activated receptor γ coactivator α (PGC1α), a master regulator of mitochondrial and peroxisomal biogenesis (12), is a transcriptional coregulator of UCP1 gene expression involved in the control of adaptive thermogenesis (13)(14)(15). Activation of PGC1α can have beneficial effects in aging in pathological conditions affecting such tissues as heart, brain, and skeletal muscle (16,17).…”