Dietary Blueberry Attenuates Whole-Body Insulin Resistance in High Fat-Fed Mice by Reducing Adipocyte Death and Its Inflammatory Sequelae

Abstract

Adipose tissue (AT) inflammation promotes insulin resistance (IR) and other obesity complications. AT inflammation and IR are associated with oxidative stress, adipocyte death, and the scavenging of dead adipocytes by proinflammatory CD11c+ AT macrophages (ATMPhi). We tested the hypothesis that supplementation of an obesitogenic (high-fat) diet with whole blueberry (BB) powder protects against AT inflammation and IR. Male C57Bl/6j mice were maintained for 8 wk on 1 of 3 diets: low-fat (10% of energy) diet (LFD), high-fat (60% of energy) diet (HFD) or the HFD containing 4% (wt:wt) whole BB powder (1:1 Vaccinium ashei and V. corymbosum) (HFD+B). BB supplementation (2.7% of total energy) did not affect HFD-associated alterations in energy intake, metabolic rate, body weight, or adiposity. We observed an emerging pattern of gene expression in AT of HFD mice indicating a shift toward global upregulation of inflammatory genes (tumor necrosis factor-alpha, interleukin-6, monocyte chemoattractant protein 1, inducible nitric oxide synthase), increased M1-polarized ATMPhi (CD11c+), and increased oxidative stress (reduced glutathione peroxidase 3). This shift was attenuated or nonexistent in HFD+B-fed mice. Furthermore, mice fed the HFD+B were protected from IR and hyperglycemia coincident with reductions in adipocyte death. Salutary effects of BB on adipocyte physiology and ATMPhi gene expression may reflect the ability of BB anthocyanins to alter mitogen-activated protein kinase and nuclear factor-kappaB stress signaling pathways, which regulate cell fate and inflammatory genes. These results suggest that cytoprotective and antiinflammatory actions of dietary BB can provide metabolic benefits to combat obesity-associated pathology.

Coenzyme Q10 supplementation lowers hepatic oxidative stress and inflammation associated with diet-induced obesity in mice

“…In another study, anti-inflammatory properties of CoQ10 on serum CRP levels of baboons have also been observed, but only when combined with vitamin E. This modification of serum CRP level was associated with an increase blood total antioxidant status [54]. Recently, Carmona et al [16] showed that i. anthocyanin induce a decrease in adipose tissue inflammation which is associated with a reduction of insulin resistance [55].…”

Postprandial hyperglycemia and insulin response are affected by sea buckthorn (Hippophaë rhamnoides ssp. turkestanica) berry and its ethanol-soluble metabolites

“…In a recent study, the inclusion of cinnamon in a rice pudding meal lowered the postprandial glucose response (Hlebowicz et al, 2007). Moreover, blueberries were reported to have potential in the attenuation of insulin resistance in an animal trial (DeFuria et al, 2009). Some exotic fruits or their phenolic extracts have also shown positive effects on sugar metabolism in animal models, as Zunino (2009) recently reviewed.…”

Wild blueberries attenuate risk factors of the metabolic syndrome

“…Feeding anthocyanin-rich extracts to mice on a high-fat diet resulted in decreased TNF-␣ expression [19,20], and the same outcome was observed in mice adipocytes when 4% whole blueberry powder was added for 8 weeks to a high-fat diet [21]. In hypercholesterolemic humans, decreased levels of serum CRP were measured in after 24 weeks of consumption of a purified anthocyanin mixture (320 mg twice a day) [22].…”