Manipulation of Dietary Amino Acids Prevents and Reverses Obesity in Mice Through Multiple Mechanisms That Modulate Energy Homeostasis

Abstract

Reduced activation of energy metabolism increases adiposity in humans and other mammals. Thus, exploring dietary and molecular mechanisms able to improve energy metabolism is of paramount medical importance because such mechanisms can be leveraged as a therapy for obesity and related disorders. Here, we show that a designer protein-deprived diet enriched in free essential amino acids can 1 ) promote the brown fat thermogenic program and fatty acid oxidation, 2 ) stimulate uncoupling protein 1 (UCP1)-independent respiration in subcutaneous white fat, 3 ) change the gut microbiota composition, and 4 ) prevent and reverse obesity and dysregulated glucose homeostasis in multiple mouse models, prolonging the healthy life span. These effects are independent of unbalanced amino acid ratio, energy consumption, and intestinal calorie absorption. A brown fat-specific activation of the mechanistic target of rapamycin complex 1 seems involved in the diet-induced beneficial effects, as also strengthened by in vitro experiments. Hence, our results suggest that brown and white fat may be targets of specific amino acids to control UCP1-dependent and -independent thermogenesis, thereby contributing to the improvement of metabolic health.

Protein quality and quantity influence the effect of dietary fat on weight gain and tissue partitioning via host-microbiota changes

“…For example, WPI intake increased the abundance of cecal B. uniformis and A. muciniphila, both of which have been shown to alleviate immunological and metabolic dysfunction in mice with HFD-induced obesity (Everard et al, 2013;Gauffin Cano et al, 2012). In further support of a link between diet, microbiota, and host metabolic responses, a recent study by Ruocco et al (2020) showed that a designer diet in which CAS-derived amino acids were substituted with a mixture of EAAs could prevent and reverse obesity in mice. In agreement with our study, the metabolic effects of EEA-rich diets were achieved independent of EI and were dependent on the gut microbiota changes.…”

Xuanbai Chengqi Decoction Ameliorates Pulmonary Inflammation via Reshaping Gut Microbiota and Rectifying Th17/Treg Imbalance in a Murine Model of Chronic Obstructive Pulmonary Disease

“… 60–62 Allobaculum has been associated previously with human diseases such as enteritis, insulin resistance, and adipose inflammation. 63 , 64 Additionally, the proportions of Tyzzerela_3 within Lachnospiraceae and Subdoligranulum within Ruminicoccaceae were also decreased in COPD mice. Inhabitants belonging to these families were generally considered to be able to digest refractory carbohydrates to generate short-chain fatty acids, 65 which can maintain barrier function, reduce inflammation in the intestine, and govern the Th17/Treg balance.…”

The Main Anthocyanin Monomer from Lycium ruthenicum Murray Fruit Mediates Obesity via Modulating the Gut Microbiota and Improving the Intestinal Barrier

“…The relative abundance of Bifidobacteriaceae was increased by P3G-FMT treatment, and the relative abundances of Streptococcaceae and Erysipelotrichaceae were decreased by P3G-FMT treatment ( Figure 7 B–D). Moreover, P3G-FMT treatment resulted in an increase in the Allobaculum genus ( Figure 7 F), which is negatively correlated with obesity [ 69 ]. Based on those results, only a slight improvement in lipid between the two groups was found.…”