L-Leucine Improves Metabolic Disorders in Mice With in-utero Cigarette Smoke Exposure

Abstract

Objectives: Maternal cigarette smoke exposure (SE) causes intrauterine undernutrition, resulting in increased risk for metabolic disorders and type 2 diabetes in the offspring without sex differences. L-leucine supplementation has been shown to reduce body weight and improve glucose metabolism in both obese animals and humans. In this study, we aimed to determine whether postnatal L-leucine supplementation in female offspring can ameliorate the detrimental impact of maternal SE.Methods: Female Balb/c mice (6-week) were exposed to cigarette smoke (SE, 2 cigarettes/day) prior to mating for 5 weeks until the pups weaned. Sham dams were exposed to air during the same period. Half of the female offspring from the SE and SHAM dams were supplied with L-leucine via drinking water (1.5% w/w) after weaning (21-day) for 10 weeks and sacrificed at 13 weeks (adulthood).Results: Maternal SE during pregnancy resulted in smaller body weight and glucose intolerance in the offspring. L-leucine supplement in Sham offspring reduced body weight, fat mass, and fasting blood glucose levels compared with their untreated littermates; however somatic growth was not changed. L-leucine supplement in SE offspring improved glucose tolerance and reduced fat mass compared with untreated littermates.Conclusions: Postnatal L-leucine supplement could reduce fat accumulation and ameliorate glucose metabolic disorder caused by maternal SE. The application of leucine may provide a potential strategy for reducing metabolic disorders in offspring from mothers who continued to smoke during pregnancy.

Integrated proteomic and metabolomic profiling of urine of renal anemia patients uncovers the molecular mechanisms of roxadustat

“…A previous study showed that quercetin transiently increased energy expenditure in mice, 27 and l -leucine was closely connected with energy balance. 28,29 Consistent with the literature, we found that “cholesterol metabolism (hsa04979)” and “glycerophospholipid metabolism (hsa00564)” were enriched during the integrated proteomics and metabolomics analysis. Taken together, our observations suggest that Roxadustat may regulate blood lipid levels by controlling the lipid metabolic pathways in renal anemia patients.…”

“…Metabolomics-based investigations revealed that Roxadustat changed the levels of urine metabolites related to fat metabolism, such as Quercetin and L-Leucine. A previous study showed that quercetin transiently increased energy expenditure in mice 27 , and L-Leucine was closely connected with energy balance 28,29 . Consistent with the literature, we found that "Cholesterol metabolism (hsa04979)" and "Glycerophospholipid metabolism (hsa00564)" were enriched during the integrated proteomics and metabolomics analysis.…”

Silica nanoparticles aggravated the metabolic associated fatty liver disease through disturbed amino acid and lipid metabolisms-mediated oxidative stress

“…Liver is a critical organ for amino acid homeostasis, thereby confirming with our findings of declined levels of a series of amino acids in the SiNPs-administered liver and highlighting how disturbed amino acid metabolism can exacerbate hepatic injury. It is increasingly recognized that abnormality in amino acids could potentially impact energy metabolism, protein synthesis and proteolysis, fatty acid and urea synthesis, and cell signaling [ [54] , [55] , [56] , [57] ]. Increased evidence suggested a close link between imbalanced amino acid homeostasis and liver diseases.…”

“…Studies have gradually revealed the roles of amino acids in oxidative stress and liver diseases. For example, l -Leucine could protect DNA damage from oxidative stress as a free radical scavenger [ 88 ], and reverse fat accumulation and metabolic disorder in Balb/c mice caused by cigarette [ 57 ]. Gamma aminobutyric acid (GABA) can reduce the oxidative stress and prevent obesity in C57BL/6 mice fed with HFD [ 89 ].…”