She P, Van Horn C, Reid T, Hutson SM, Cooney RN, Lynch CJ. Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched-chain amino acid metabolism.

Leucine is recognized as a nutrient signal; however, the long-term in vivo consequences of leucine signaling and the role of branched-chain amino acid (BCAA) metabolism in this signaling remain unclear. To investigate these questions, we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism. BCATm(-/-) mice exhibited elevated plasma BCAAs and decreased adiposity and body weight, despite eating more food, along with increased energy expenditure, remarkable improvements in glucose and insulin tolerance, and protection from diet-induced obesity. The increased energy expenditure did not seem to be due to altered locomotor activity, uncoupling proteins, sympathetic activity, or thyroid hormones but was strongly associated with food consumption and an active futile cycle of increased protein degradation and synthesis. These observations suggest that elevated BCAAs and/or loss of BCAA catabolism in peripheral tissues play an important role in regulating insulin sensitivity and energy expenditure.

mixtures of cis -9, trans -11 (9,11) conjugated linoleic acid (CLA) and trans -10, cis -12 (10,12) CLA. Indeed, consuming a mixture of these CLA isomers, or 10,12 CLA alone, reduced body fat in many animal (reviewed in Ref. 3 ) and human studies ( 4 ). Rodents that consumed higher amounts of the CLA than humans (e.g., 0.5-1.5% CLA in the diet or 600-1,800 mg/kg body weight) lost body fat more rapidly but concurrently developed side effects, including chronic infl ammation, insulin resistance, and lipoatrophy ( 5 ). Notably, intermediate levels of mixed CLA isomers (i.e., 0.1-0.3%, w/w) reduced adiposity in mice without adversely affecting liver weight or lipid content ( 6 ). However, individual isomers were not fed, the level of reduction in adiposity in the 0.1% group was marginal, and anti-obesity mechanisms were not identifi ed ( 6 ). In contrast, clinical trials routinely use lower doses of CLA (e.g., 3-6 g/day or 35-70 mg/kg body weight), although the relative decrease in adiposity is not as rapid or great as in the higher doses used in rodent studies.It has been reported that only the 10,12 CLA isomer reduces adiposity or delipidates adipocytes; however, at relatively high doses it also causes adverse side effects in Abstract The objective of this study was to examine the mechanism by which conjugated linoleic acid (CLA) reduces body fat. Young male mice were fed three combinations of fatty acids at three doses (0.06%, 0.2%, and 0.6%, w/w) incorporated into AIN76 diets for 7 weeks. The types of fatty acids were linoleic acid (control), an equal mixture of trans -10, cis -12 (10,12) CLA plus linoleic acid, and an equal isomer mixture of 10,12 plus cis -9, trans -11 (9,11) CLA. Mice receiving the 0.2% and 0.6% dose of 10,12 CLA plus linoleic acid or the CLA isomer mixture had decreased white adipose tissue (WAT) and brown adipose tissue (BAT) mass and increased incorporation of CLA isomers in epididymal WAT and liver. Notably, in mice receiving 0.2% of both CLA treatments, the mRNA levels of genes associated with browning, including uncoupling protein 1 (UCP1), UCP1 protein levels, and cytochrome c oxidase activity, were increased in epididymal WAT. CLA-induced browning in WAT was accompanied by increases in mRNA levels of markers of infl ammation. Muscle cytochrome c oxidase activity and BAT UCP1 protein levels were not affected by CLA treatment. These data suggest a linkage between decreased adiposity, browning in WAT, and low-grade infl ammation due to consumption of 10,12 CLA.

There is a need for effective wound treatments that retain the bioactivity of a cellular treatment, but without the high costs and complexities associated with manufacturing, storing, and applying living biological products. Previously, we developed an amnion membrane-derived hydrogel and evaluated its wound healing properties using a mouse wound model. In this study, we used a full thickness porcine skin wound model to evaluate the wound-healing efficacy of the amnion hydrogel and a less-processed amnion product comprising a lyophilized amnion membrane powder. These products were compared with commercially available amnion and nonamnion wound healing products. We found that the amnion hydrogel and amnion powder treatments demonstrated significant and rapid wound healing, driven primarily by new epithelialization versus closure by contraction. Histological analysis demonstrated that these treatments promote the formation of a mature epidermis and dermis with similar composition to healthy skin. The positive skin regenerative outcomes using amnion hydrogel and amnion powder treatments in a large animal model further demonstrate their potential translational value for human wound treatments.