Improve Metabolism Disorder Research Articles

Effects of methionine intake on cognitive function in mild cognitive impairment patients and APP/PS1 Alzheimer's Disease model mice: Role of the cystathionine-β-synthase/H2S pathway

As a dietary intervention, methionine restriction (MR) has been reported to increase longevity and improve metabolism disorders. However, the effects of MR on alleviating neurodegenerative diseases such as Alzheimer's disease (AD) are largely unexplored. Here we sought to investigate the neuroprotective effects of low methionine intake in mild cognitive impairment (MCI) patients and APP/PS1 AD model mice, and to uncover the underlying mechanisms. In a cohort composed of 45 individuals diagnosed with MCI and 61 healthy controls without cognitive impairment, methionine intake was found to be positively associated with the increased risk of MCI, where no sex differences were observed. We further conducted a 16-week MR intervention (0.17% methionine, w/w) on APP/PS1 AD model mice. Although MR reduced Aβ accumulation in the brain of both male and female APP/PS1 mice, MR improved cognitive function only in male mice, as assessed by the Morris water maze test. Consistently, MR restored synapse ultrastructure and alleviated mitochondrial dysfunction by enhancing mitochondrial biogenesis in the brain of male APP/PS1 mice. Importantly, MR effectively balanced the redox status and activated cystathionine-β-synthase (CBS)/H2S pathway in the brain of male APP/PS1 mice. Together, our study indicated that lower dietary methionine intake is associated with improved cognitive function, in which CBS/H2S pathway plays an essential role. MR could be a promising nutritional intervention for preventing AD development.

Pharmacological inhibition of diacylglycerol acyltransferase 1 reduces body weight gain, hyperlipidemia, and hepatic steatosis in db/db mice

To test whether pharmacological inhibition of Diacylglycerol acyltransferase 1 (DGAT1) by a small-molecule inhibitor H128 can improve metabolism disorders in leptin receptor-deficient db/db mice. To investigate the effect of H128 on intestinal fat absorption,db/db mice were acutely given a bolus of corn oil by gavage. The mice were further orally administered H128 (3 and 10 mg/kg) for 5 weeks. Blood glucose, lipids, insulin, ALT, and AST as well as hepatic triglycerides were measured. The insulin tolerance test was performed to evaluate insulin sensitivity. The expression of genes involved in fatty acid oxidation was detected by RT-PCR. Oral administration of H128 (10 mg/kg) acutely inhibited intestinal fat absorption following a lipid challenge in db/db mice. Chronic treatment with H128 significantly inhibited body weight gain, decreased food intake, and induced a pronounced reduction of serum triglycerides. In addition, H128 treatment markedly ameliorated hepatic steatosis, characterized by decreased liver weight, lipid droplets, and triglyceride content as well as serum ALT and AST levels. Furthermore, H128 treatment increased the expression of the CPT1 and PPARα genes in liver, suggesting that H128 enhanced fatty acid oxidation in db/db mice. However, neither blood glucose nor insulin tolerance was affected by H128 treatment throughout the 5-week experimental period. DGAT1 may be an effective therapeutic target for the treatment of obesity, hyperlipidemia and hepatic steatosis.