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

Chwan-Li Shen,Latha Ramalingam,Michael D Tomison,Naima Moustaid-Moussa,Shaligram Sharma,Jannette M Dufour,Desiree Wanders,Eunhee Chung,Gurvinder Kaur,Huanbiao Mo

doi:10.1038/s41598-018-29063-9

Abstract

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.

Highlights

Diabetes mellitus (DM) is a chronic metabolic disorder that affects more than 30.3 million people in the United States; an additional 84.1 million individuals have been diagnosed with prediabetes[1]
We focused on the beneficial effect of annatto-extracted TT on glucose homeostasis and bone health in a high-fat diet (HFD)-induced type 2 DM (T2DM) model
At the end of the 14-week study, the statistical results showed the order of body weight as follows: T1600 group = HFD group = T400 group >metformin (Met) group >low-fat diet (LFD) group (p < 0.001)

Summary

Introduction

Diabetes mellitus (DM) is a chronic metabolic disorder that affects more than 30.3 million people in the United States; an additional 84.1 million individuals have been diagnosed with prediabetes[1]. Oxidative stress and chronic inflammation have detrimental effects on skeletal muscle, pancreatic beta cells, and bone[2,12,13], causing imbalance in bone metabolism and bone loss[2,12,13,14]. Preclinical studies have shown the effect of a mixture of TT on glucose homeostasis in STZ-treated type 1 DM animals through down-regulation of transforming growth factor-β18 or suppression of oxidative stress[19]. With its strong anti-oxidative/anti-inflammatory properties, annatto-extracted TT, consisting of 90% δ -TT and 10% γ -TT, would be a good candidate to evaluate TT’s effects on T2DM-related complications, such as hyperglycemia and bone deterioration. We hypothesized that annatto-extracted TT has both anti-diabetic and anti-osteoporotic properties in HFD-induced T2DM animals through suppression of inflammation

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Conclusion