Berries as a Treatment for Obesity-Induced Inflammation: Evidence from Preclinical Models.

Inflammation that accompanies obesity is associated with the infiltration of metabolically active tissues by inflammatory immune cells. This propagates a chronic low-grade inflammation associated with increased signaling of common inflammatory pathways such as NF-κB and Toll-like receptor 4 (TLR4). Obesity-associated inflammation is linked to an increased risk of chronic diseases, including type 2 diabetes, cardiovascular disease, and cancer. Preclinical rodent and cell culture studies provide robust evidence that berries and their bioactive components have beneficial effects not only on inflammation, but also on biomarkers of many of these chronic diseases. Berries contain an abundance of bioactive compounds that have been shown to inhibit inflammation and to reduce reactive oxygen species. Therefore, berries represent an intriguing possibility for the treatment of obesity-induced inflammation and associated comorbidities. This review summarizes the anti-inflammatory properties of blackberries, blueberries, strawberries, and raspberries. This review highlights the anti-inflammatory mechanisms of berries and their bioactive components that have been elucidated through the use of preclinical models. The primary mechanisms mediating the anti-inflammatory effects of berries include a reduction in NF-κB signaling that may be secondary to reduced oxidative stress, a down-regulation of TLR4 signaling, and an increase in Nrf2.

Annatto-extracted tocotrienols improve glucose homeostasis and bone properties in high-fat diet-induced type 2 diabetic mice by decreasing the inflammatory response.

Diabetes is a risk factor for osteoporosis. Annatto-extracted tocotrienols (TT) have proven benefits in preserving bone matrix. Here, we evaluated the effects of dietary TT on glucose homeostasis, bone properties, and liver pro-inflammatory mRNA expression in high-fat diet (HFD)-induced type 2 diabetic (T2DM) mice. 58 male C57BL/6 J mice were divided into 5 groups: low-fat diet (LFD), HFD, HFD + 400 mgTT/kg diet (T400), HFD + 1600 mgTT/kg diet (T1600), and HFD + 200 mg metformin/kg (Met) for 14 weeks. Relative to the HFD group, both TT-supplemented groups (1) improved glucose homeostasis by lowering the area under the curve for both glucose tolerance and insulin tolerance tests, (2) increased serum procollagen I intact N-terminal propeptide (bone formation) level, trabecular bone volume/total volume, trabecular number, connectivity density, and cortical thickness, (3) decreased collagen type 1 cross-linked C-telopeptide (bone resorption) levels, trabecular separation, and structure model index, and (4) suppressed liver mRNA levels of inflammation markers including IL-2, IL-23, IFN-γ, MCP-1, TNF-α, ITGAX and F4/80. There were no differences in glucose homeostasis and liver mRNA expression among T400, T1600, and Met. The order of osteo-protective effects was LFD ≥T1600 ≥T400 = Met >HFD. Collectively, these data suggest that TT exerts osteo-protective effects in T2DM mice by regulating glucose homeostasis and suppressing inflammation.

Metabolic responses to dietary leucine restriction involve remodeling of adipose tissue and enhanced hepatic insulin signaling.

Dietary leucine was incrementally restricted to test whether limiting this essential amino acid (EAA) would fully reproduce the beneficial responses produced by dietary methionine restriction. Restricting leucine by 85% increased energy intake and expenditure within 5 to 7 days of its introduction and reduced overall accumulation of adipose tissue. Leucine restriction (LR) also improved glucose tolerance, increased hepatic release of fibroblast growth factor 21 into the blood stream, and enhanced insulin-dependent activation of Akt in liver. However, LR had no effect on hepatic lipid levels and failed to lower lipogenic gene expression in the liver. LR did affect remodeling of white and brown adipose tissues, increasing expression of both thermogenic and lipogenic genes. These findings illustrate that dietary LR reproduces many but not all of the physiological responses of methionine restriction. The primary differences occur in the liver, where methionine and LR cause opposite effects on tissue lipid levels and expression of lipogenic genes. Altogether, these findings suggest that the sensing systems which detect and respond to dietary restriction of EAAs act through mechanisms that both leucine and methionine are able to engage, and in the case of hepatic lipid metabolism, may be unique to specific EAAs such as methionine.

Lipid-lowering drugs and circulating adiponectin.

Pharmacological agents used to treat primary and combined hyperlipidemia reduce cardiovascular disease morbidity and mortality. Risk reduction has been attributed to improvements in blood lipid and lipoprotein characteristics. However, each class of available lipid-lowering drugs has been shown to exhibit pleiotropic effects that broaden their anticipated actions. Indeed, the results of a growing number of available studies suggest that a strong relationship exists between pharmacological reductions in blood lipids and circulating concentrations of the adipose tissue derived protein, adiponectin. Adiponectin is the most abundantly secreted protein from adipose tissue and has been shown to decrease hepatic glucose production, increase fatty acid oxidation in liver and skeletal muscle, and decrease vascular inflammation. In this chapter, we present a comprehensive analysis of the effects of the available classes of lipid-lowering drugs (statins, fibrates, niacin, and omega-3-fatty acids) on circulating adiponectin and the known mechanisms which produce these important events.