Abstract

Beginning at 16 weeks of age and continuing for 44 weeks, male C57BL/6J were fed either a control (CON) diet; a high-fat (HF) diet (60% unsaturated); or the HF diet containing an extract of unripe avocados (AvX) enriched in the 7-carbon sugar mannoheptulose (MH), designed to act as a glycolytic inhibitor (HF + MH). Compared to the CON diet, mice on the HF diet exhibited higher body weights; body fat; blood lipids; and leptin with reduced adiponectin levels, insulin sensitivity, VO2max, and falls from a rotarod. Mice on the HF + MH diet were completely protected against these changes in the absence of significant diet effects on food intake. Compared to the CON diet, oxidative stress was also increased by the HF diet indicated by higher levels of total reactive oxygen species, superoxide, and peroxynitrite measured in liver samples by electron paramagnetic resonance spectroscopy, whereas the HF + MH diet attenuated these changes. Compared to the CON, the HF diet increased signaling in the mechanistic target of the rapamycin (mTOR) pathway, and the addition of the MH-enriched AvX to this diet attenuated these changes. Beyond generating further interest in the health benefits of avocados, these results draw further new attention to the effects of this rare sugar, MH, as a botanical intervention for preventing obesity.

Highlights

  • Obesity is viewed as one of the major factors contributing to morbidity and mortality in industrialized nations, and the rate of this condition has been increasing dramatically over the past several years in these populations [1,2]

  • The current study examined a botanical intervention focusing on a novel approach to obesity prevention, the inhibition of intracellular glucose metabolism

  • The HF diet induced significant gains in body weight from baseline, showing statistical significance beginning at 4 weeks on the diet compared to the CON group (Figure 1A)

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Summary

Introduction

Obesity is viewed as one of the major factors contributing to morbidity and mortality in industrialized nations, and the rate of this condition has been increasing dramatically over the past several years in these populations [1,2]. Many botanical interventions have been proposed and marketed, but few have strong clinical support [4]. Watanabe et al [5] provided a recent systematic review of dietary supplements/botanicals claiming to have weight control effects. They rated the quality of the evidence for such claims as low, moderate, or high. None of the candidates were rated to have a high quality of evidence to support claims. Grouped by proposed mechanism of action, the following candidates were rated to have a moderate quality of evidence: (a) Nutrient Absorption: green tea, white kidney beans; (b) Appetite Suppression: whey protein, caffeine; (c) Energy Expenditure: dyacilglycerol; and (d) Carbohydrate Metabolism: chromium

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