Peroxisome Proliferator–Activated Receptor (PPAR)α Activation Increases Adiponectin Receptors and Reduces Obesity-Related Inflammation in Adipose Tissue

Abstract

We examined the effects of activation of peroxisome proliferator-activated receptor (PPAR)␣, PPAR␥, and both of them in combination in obese diabetic KKAy mice and investigated the mechanisms by which they improve insulin sensitivity. PPAR␣ activation by its agonist, Wy-14,643, as

Fenofibrate and pioglitazone improve endothelial function and reduce arterial stiffness in obese glucose tolerant men

“…Similar to the current study Tsigos et al reported that plasma TNF␣ positively correlates with abdominal obesity [15]; however, there is no consensus about the contribution of fat depots to circulating levels of TNF␣ [14]. The increase in pro-inflammatory cytokines in adipose tissue is closely linked to the increase in adipose tissue resident macrophages [16]. The thiazolidinediones (TZDs) are known to have anti-inflammatory properties; one of the TZDs, rosiglitazone, has been shown to reduce the number of macrophages in white adipose tissue in mice [16], and hence to reduced macrophage-derived inflammatory cytokines.…”

“…The increase in pro-inflammatory cytokines in adipose tissue is closely linked to the increase in adipose tissue resident macrophages [16]. The thiazolidinediones (TZDs) are known to have anti-inflammatory properties; one of the TZDs, rosiglitazone, has been shown to reduce the number of macrophages in white adipose tissue in mice [16], and hence to reduced macrophage-derived inflammatory cytokines. TZDs also promote adipocyte differentiation and it is suggested that the smaller adipocytes which result from this are more insulin sensitive than large adipocytes [17].…”

“…Control [9] Placebo [15] Pioglitazone [16] Fenofibrate [16] Fasting insulin (mU/ml) Integrated insulin response was calculated using area under the curve (AUC) of serum insulin at 30 min intervals up to 180 min during 75 g OGTT. Fasting insulin and insulin AUC values were transformed to natural logarthims for statistical analysis.…”

Physiological and pathophysiological roles of adiponectin and adiponectin receptors in the integrated regulation of metabolic and cardiovascular diseases

“…22 We then developed an enzyme-linked immunosorbent assay for specific measurement of human HMW adiponectin. 23 The HMW adiponectin/total adiponectin ratio is more tightly correlated with insulin resistance than total adiponectin.…”

“…22 We next searched for strategies that could increase HMW adiponectin and found that a PPARg agonist and energy restriction upregulated the reduced HMW adiponectin. 22 Next, we attempted to clarify the relative contribution of adiponectin in the actions, such as antidiabetic effects, of a PPARg agonist. 25 In all, 10 mg kg À1 pioglitazone significantly ameliorated diabetes in ob/ob mice, but not in adiponectin deficient ob/ob mice.…”