Decreased AMP-activated protein kinase activity is associated with increased inflammation in visceral adipose tissue and with whole-body insulin resistance in morbidly obese humans

Abstract

Inflammation and infiltration of immune cells in white adipose tissue have been implicated in the development of obesity-associated insulin resistance. Likewise, dysregulation of the fuel-sensing enzyme AMP-activated protein kinase (AMPK) has been proposed as a pathogenetic factor for these abnormalities based on both its links to insulin action and its anti-inflammatory effects. In this study, we examined the relationships between AMPK activity, the expression of multiple inflammatory markers in visceral (mesenteric and omental) and abdominal subcutaneous adipose tissue, and whole-body insulin sensitivity in morbidly obese patients (BMI 48 ± 1.9 kg/m2) undergoing gastric bypass surgery. AMPK activity was assessed by western-blots (P-AMPK/T-AMPK) and mRNA levels of various markers of inflammation by qRT-PCR. Patients were stratified as insulin sensitive obese or insulin resistant obese according to their HOMA-IR values. The results indicate that AMPK activity is lower in visceral than in subcutaneous abdominal adipose tissue of these patients and that this is associated with an increased expression of multiple inflammatory genes. They also revealed that AMPK activity is lower in adipose tissue of obese patients who are insulin resistant (HOMA-IR > 2.3) than in BMI-matched insulin sensitive subjects. Furthermore, this difference was evident in all three fat depots. In conclusion, the data suggest that there are close links between reduced AMPK activity and inflammation in white adipose tissue, and whole-body insulin resistance in obese humans. Whether adipose tissue AMPK dysregulation is a causal factor for the development of the inflammation and insulin resistance remains to be determined.

Reduced Socs3 expression in adipose tissue protects female mice against obesity-induced insulin resistance

“…Socs3 AKO mice have similar adiposity, adipose-tissue cell size SOCS3 has been proposed to be a negative regulator of leptin signalling in adipocytes [8]; consistent with this idea, recent studies have shown that AMPK activity is reduced in adipose tissue with obesity [23,24]. We hypothesised that AMPK activity might be elevated in adipose tissue of Socs3 AKO mice and that this might be associated with reductions in adipose-tissue cell size.…”

“…This activation of AMPK is associated with the rapid depletion of lipid from adipocytes and results in increases in glycerol but not NEFA, suggesting that leptin reduces adipose tissue mass by increasing the rate of adipose tissue fatty-acid oxidation [21,22]. Consistent with the potential for SOCS3 to inhibit adipose tissue leptin signalling, recent reports in both rodents [23] and humans [24] have found that AMPK phosphorylation is reduced with obesity.…”

Plasma 8-Isoprostane Concentrations and Adipogenic and Adipokine Gene Expression Patterns in Subcutaneous and Mesenteric Adipose Tissues of Fattening <i>Wagyu</i> Cattle

“…The present study indicated that a higher intake of dietary α-tocopherol reduces the expressions of the adipogenic (C/EBPβ, C/EBPδ and C/EBPα) and adipokine (VEGF, FGF-2, leptin and adiponectin) genes in mesenteric adipose tissue with the reduction of plasma 8-isoprostane levels. Studies on the regional differences of adipose tissue showed that visceral adipose tissue, when compared to subcutaneous adipose tissue, plays a key role in elevating the risk of metabolic syndrome with increased inflammation in humans [10,12,29]. The expression of inflammatory mediator adipokines in visceral adipose tissue is higher than that in subcutaneous adipose tissue [4,9].…”

Adipocytes, aldosterone and obesity-related hypertension

“…Alternatively, this effect may represent a mechanism in the autoregulation of adipose tissue perfusion during starvation, when adipocyte-secreted vasoactive factors may be required without influencing systemic blood pressure. Considering that AMPK activity is reduced in adipose tissue of insulin-resistant obese patients undergoing bariatric surgery (Gauthier et al 2011), it is likely that this mechanism may not be relevant in such individuals and therefore may represent a dynamic physiological rather than chronic pathophysiological regulation of adipocyte aldosterone secretion. One study assessed the effect of AICAR on adrenal steroidogenesis focussing on androgen production.…”