Pecans and Its Polyphenols Prevent Obesity, Hepatic Steatosis and Diabetes by Reducing Dysbiosis, Inflammation, and Increasing Energy Expenditure in Mice Fed a High-Fat Diet.

Pecans (Carya illinoinensis) are considered a functional food due to the high content of polyunsaturated fatty acids, dietary fiber and polyphenols. To determine the effect of whole pecans (WP) or a pecan polyphenol (PP) extract on the development of metabolic abnormalities in mice fed a high-fat (HF) diet, we fed C57BL/6 mice with a Control diet (7% fat), HF diet (23% fat), HF containing 30% WP or an HF diet supplemented with 3.6 or 6 mg/g of PP for 18 weeks. Supplementation of an HF diet with WP or PP reduced fat mass, serum cholesterol, insulin and HOMA-IR by 44, 40, 74 and 91%, respectively, compared to the HF diet. They also enhanced glucose tolerance by 37%, prevented pancreatic islet hypertrophy, and increased oxygen consumption by 27% compared to the HF diet. These beneficial effects were associated with increased thermogenic activity in brown adipose tissue, mitochondrial activity and AMPK activation in skeletal muscle, reduced hypertrophy and macrophage infiltration of subcutaneous and visceral adipocytes, reduced hepatic lipid content and enhanced metabolic signaling. Moreover, the microbial diversity of mice fed WP or PP was higher than those fed HF, and associated with lower circulating lipopolysaccharides (~83-95%). Additionally, a 4-week intervention study with the HF 6PP diet reduced the metabolic abnormalities of obese mice. The present study demonstrates that WP or a PP extract prevented obesity, liver steatosis and diabetes by reducing dysbiosis, inflammation, and increasing mitochondrial content and energy expenditure. Pecan polyphenols were mainly condensed tannin and ellagic acid derivatives including ellagitannins as determined by LC-MS. Herein we also propose a model for the progression of the HF diet-mediated metabolic disorder based on early and late events, and the possible molecular targets of WP and PP extract in preventive and intervention strategies. The body surface area normalization equation gave a conversion equivalent to a daily human intake dose of 2101-3502 mg phenolics that can be obtained from 110-183 g pecan kernels/day (22-38 whole pecans) or 21.6-36 g defatted pecan flour/day for an average person of 60 kg. This work lays the groundwork for future clinical studies.

The capacity of differentiation of stromal vascular fraction cells into beige adipocytes is markedly reduced in subjects with overweight/obesity and insulin resistance: effect of genistein.

BACKGROUND: Dietary bioactive compounds have been demonstrated to produce several health benefits. Genistein, an isoflavone of soy protein, and resveratrol, a polyphenol from grapes, have been shown to improve insulin sensitivity and to stimulate white adipose tissue (WAT) browning, leading to increased energy expenditure. However, it has not been demonstrated in humans whether genistein or resveratrol have the capacity to stimulate the differentiation of stromal vascular fraction (SVF) cells from white fat into beige adipocytes. SUBJECTS/METHODS: With this aim, we assessed whether stromal vascular fraction cells obtained from biopsies of the subdermal fat depots of subjects with normal body weight (NW) or from subjects with overweight/obesity with (OIR) or without (OIS) insulin resistance were able to differentiate into the beige adipose tissue lineage in vitro, by exposing the cells to genistein, resveratrol, or the combination of both. RESULTS: The results showed that SVF cells obtained from NW or OIS subjects were able to differentiate into beige adipocytes according to an increased expression of beige biomarkers including UCP1, PDRM-16, PGC1α, CIDEA, and SHOX2 upon exposure to genistein. However, SVF cells from OIR subjects were unable to differentiate into beige adipocytes with any of the inducers. Exposure to resveratrol or the combination of resveratrol/genistein did not significantly stimulate the expression of browning markers in any of the groups studied. We found that the non-responsiveness of the SVF from subjects with obesity and insulin resistance to any of the inducers was associated with an increase in the expression of endoplasmic reticulum stress markers. CONCLUSION: Consumption of genistein may stimulate WAT browning mainly in NW or OIS subjects. Thus, obesity associated with insulin resistance may be considered as a condition that prevents some beneficial effects of some dietary bioactive compounds.

Goat's Milk Intake Prevents Obesity, Hepatic Steatosis and Insulin Resistance in Mice Fed A High-Fat Diet by Reducing Inflammatory Markers and Increasing Energy Expenditure and Mitochondrial Content in Skeletal Muscle.

Goat's milk is a rich source of bioactive compounds (peptides, conjugated linoleic acid, short chain fatty acids, monounsaturated and polyunsaturated fatty acids, polyphenols such as phytoestrogens and minerals among others) that exert important health benefits. However, goat's milk composition depends on the type of food provided to the animal and thus, the abundance of bioactive compounds in milk depends on the dietary sources of the goat feed. The metabolic impact of goat milk rich in bioactive compounds during metabolic challenges such as a high-fat (HF) diet has not been explored. Thus, we evaluated the effect of milk from goats fed a conventional diet, a conventional diet supplemented with 30% Acacia farnesiana (AF) pods or grazing on metabolic alterations in mice fed a HF diet. Interestingly, the incorporation of goat's milk in the diet decreased body weight and body fat mass, improved glucose tolerance, prevented adipose tissue hypertrophy and hepatic steatosis in mice fed a HF diet. These effects were associated with an increase in energy expenditure, augmented oxidative fibers in skeletal muscle, and reduced inflammatory markers. Consequently, goat's milk can be considered a non-pharmacologic strategy to improve the metabolic alterations induced by a HF diet. Using the body surface area normalization method gave a conversion equivalent daily human intake dose of 1.4 to 2.8 glasses (250 mL per glass/day) of fresh goat milk for an adult of 60 kg, which can be used as reference for future clinical studies.