One anastomosis gastric bypass ameliorates diabetic nephropathy via regulating the GLP-1-mediated Sirt1/AMPK/PGC1α pathway.

BACKGROUND: Diabetic nephropathy (DN), a complication of diabetes, is the most leading cause of end-stage renal disease. Bariatric surgery functions on the remission of diabetes and diabetes-related complications. One anastomosis gastric bypass (OAGB), one of popular bariatric surgery, can improve diabetes and its complications by regulating the glucagon-like peptide-1 (GLP-1) level. Meanwhile, GLP-1 can alleviate renal damage in high-fat-diet-induced obese rats. However, the effect of OAGB on renal injury remains uncertain in DN. METHODS: A diabetes model was elicited in rats via HFD feeding and STZ injection. The role and mechanism of OAGB were addressed in DN rats by the body and kidney weight and blood glucose supervision, oral glucose tolerance test (OGTT), enzyme-linked immunosorbent assay (ELISA), biochemistry detection, histopathological analysis, and western blot assays. RESULTS: OAGB surgery reversed the increase in body weight and glucose tolerance indicators in diabetes rats. Also, OAGB operation neutralized the DN-induced average kidney weight, kidney weight/body weight, and renal injury indexes accompanied with reduced glomerular hypertrophy, alleviated mesangial dilation and decreased tubular and periglomerular collagen deposition. In addition, OAGB introduction reduced the DN-induced renal triglyceride and renal cholesterol with the regulation of fatty acids-related proteins expression. Mechanically, OAGB administration rescued the DN-induced expression of Sirt1/AMPK/PGC1α pathway mediated by GLP-1. Pharmacological block of GLP-1 receptor inverted the effect of OAGB operation on body weight, glucose tolerance, renal tissue damage, and fibrosis and lipids accumulation in DN rats. CONCLUSION: OAGB improved renal damage and fibrosis and lipids accumulation in DN rats by GLP-1-mediated Sirt1/AMPK/PGC1α pathway.

Effect of Nitrogen, Salinity, and Light Intensity on the Biomass Composition of Nephroselmis sp.: Optimization of Lipids Accumulation (Including EPA).

Microalgal biomass is characterized by high protein, carbohydrates, and lipids concentrations. However, their qualitative and quantitative compositions depend not only on the cultivated species but also on the cultivation conditions. Focusing on the microalgae's ability to accumulate significant fatty acids (FAs) amounts, they can be valorized either as dietary supplements or for biofuel production, depending on the accumulated biomolecules. In this study, a local isolate (Nephroselmis sp.) was precultured under autotrophic conditions, while the Box-Behnken experimental design followed using the parameters of nitrogen (0-250 mg/L), salinity (30-70 ppt) and illuminance (40-260 µmol m-2 s-1) to evaluate the accumulated biomolecules, with an emphasis on the amount of FAs and its profile. Regardless of the cultivation conditions, the FAs of C14:0, C16:0, and C18:0 were found in all samples (up to 8% w/w in total), while the unsaturated C16:1 and C18:1 were also characterized by their high accumulations. Additionally, the polyunsaturated FAs, including the valuable C20:5n3 (EPA), had accumulated when the nitrogen concentration was sufficient, and the salinity levels remained low (30 ppt). Specifically, EPA approached 30% of the total FAs. Therefore, Nephroselmis sp. could be considered as an alternative EPA source compared to the already-known species used in food supplementation.

Sulfur mustard analog 2-chloroethyl ethyl sulfide increases triglycerides by activating DGAT1-dependent biogenesis and inhibiting PGC1ɑ-dependent fat catabolism in immortalized human bronchial epithelial cells.

Using sulfur mustard analog 2-chloroethyl ethyl sulfide (CEES), we established an in vitro model by poisoning cultured immortalized human bronchial epithelial cells. Nile Red staining revealed lipids accumulated 24 h after a toxic dose of CEES (0.9 mM). Lipidomics analysis showed most of the increased lipids were triglycerides (TGs), and the increase in TGs was further confirmed using a Triglyceride-Glo™ Assay kit. Protein and mRNA levels of DGAT1, an important TG biogenesis enzyme, were increased following 0.4 mM CEES exposure. Under higher dose CEES (0.9 mM) exposure, protein and mRNA levels of PPARγ coactivator-1ɑ (PGC-1ɑ), a well-known transcription factor that regulates fatty acid oxidation, were decreased. Finally, application with DGAT1 inhibitor A 922500 or PGC1ɑ agonist ZLN005 was able to block the CEES-induced TGs increase. Overall, our dissection of CEES-induced TGs accumulation provides new insight into energy metabolism dysfunction upon vesicant exposure.HIGHLIGHTSIn CEES (0.9 mM)-injured cells:Triglycerides (TGs) were abundant in the accumulated lipids.Expression of DGAT1, not DGAT2, was increased.Expression of PGC1ɑ, not PGC1ß, was reduced.DGAT1 inhibitor or PGC1ɑ agonist blocked the CEES-mediated increase in TGs.

Perspectives of nervonic acid production by Yarrowia lipolytica.

Nervonic acid (cis-15-tetracosenoic acid, 24:1Δ15) is a long chain monounsaturated fatty acid, mainly exists in white matt er of the human brains. It plays an important role in the development of nervous system and curing neurological diseases. The limited natural sources and high price are considered limiting factors for the extensive application of nervonic acid. Yarrowia lipolytica is a high lipid producing yeast and engineered strain which can produce nervonic acid. The biosynthesis of nervonic acid has yet to be investigated, although the metabolism has been examined for couple of years. Normally, oleic acid is considered the origin of nervonic acid synthesis through fatty acid prolongation, where malonyl-CoA and acyl-CoA are initially concise by 3-ketoacyl-CoA synthase (KCS). To meet the high requirement of industrial production, the optimization of fermentation and bioreactors configurations are necessary tools to be carried out. This review article summarizes the research literature on advancements and recent trends about the production, synthesis and properties of nervonic acid.

Sex-dependent effects of ambient PM2.5 pollution on insulin sensitivity and hepatic lipid metabolism in mice.

BACKGROUND & AIMS: Emerging evidence supports ambient fine particulate matter (PM2.5) exposure is associated with insulin resistance (IR) and hepatic lipid accumulation. In this study, we aimed to evaluate the sex-dependent vulnerability in response to PM2.5 exposure and investigate the underlying mechanism by which PM2.5 modulates hepatic lipid metabolism. METHODS: Both male and female C57BL/6 mice were randomly assigned to ambient PM2.5 or filtered air for 24 weeks via a whole body exposure system. High-coverage quantitative lipidomics approaches and liquid chromatography-mass spectrometry techniques were performed to measure hepatic metabolites and hormones in plasma. Metabolic studies, histological analyses, as well as gene expression levels and molecular signal transduction analysis were applied to examine the effects and mechanisms by which PM2.5 exposure-induced metabolic disorder. RESULTS: Female mice were more susceptible than their male counterparts to ambient PM2.5 exposure-induced IR and hepatic lipid accumulation. The hepatic lipid profile was changed in response to ambient PM2.5 exposure. Levels of hepatic triacylglycerols (TAGs), free fatty acids (FFAs) and cholesterol were only increased in female mice from PM group compared to control group. Plasmalogens were dysregulated in the liver from PM2.5-exposed mice as well. In addition, exposure to PM2.5 led to enhanced hepatic ApoB and microsomal triglyceride transport protein expression in female mice. Finally, PM2.5 exposure inhibited hypothalamus-pituitary-adrenal (HPA) axis and decreased glucocorticoids levels, which may contribute to the vulnerability in PM2.5-induced metabolic dysfunction. CONCLUSIONS: Ambient PM2.5 exposure inhibited HPA axis and demonstrated sex-associated differences in its effects on IR and disorder of hepatic lipid metabolism. These findings provide new mechanistic evidence of hormone regulation in air pollution-mediated metabolic abnormalities of lipids and more personalized care should be considered in terms of sex-specific risk factors.

The growth, lipid accumulation and adaptation mechanism in response to variation of temperature and nitrogen supply in psychrotrophic filamentous microalga Xanthonema hormidioides (Xanthophyceae).

BACKGROUND: Microalgae are promising feedstocks for production of renewable biofuels and value-added bioproducts. Temperature and nitrogen supply are important environmental and nutritional factors affecting the growth and metabolism of microalgae, respectively. In this study, the growth and lipid accumulation of filamentous microalgae Xanthonema hormidioides under different temperatures (5, 7, 10, 15, 20, 25, 27 and 30 °C) and initial nitrogen concentrations (3, 9, 18 mM) were investigated, and its adaptive mechanisms of tolerance to low temperature and nitrogen stress were analysis by proteomics. RESULTS: The optimum temperature range for the growth of X. hormidioides was between 15 and 20 °C, and the algal cells had slow growth rate at 5 °C and could not survive at 30 °C. The maximum biomass concentration was 11.73 g L-1 under the temperature of 20 °C, and the highest total lipid content was 56.63% of dry weight. Low temperature did not change the fatty acids profiles but promoted the accumulation of unsaturated fatty acids of X. hormidioides. The maximum contents of palmitoleic acid, eicosapentaenoic acid and total fatty acid were 23.64%, 2.49% and 41.14% of dry weight, respectively. Proteomics was performed under three temperature (7, 15, 25 °C), two nitrogen concentrations (3 and 18 mM) and two cultivation times (day 3 and 12). A total of 6503 proteins were identified. In the low temperature, photosynthesis-related proteins were down-regulated to protect the photosynthetic apparatus. The up-regulation of key enzymes DGAT and PDAT demonstrated the accumulation of TAGs under low nitrogen treatment. The proteins related to ribosome, phosphatidylinositol signaling system, antioxidant system and cold shock proteins (CSPs) in X. hormidioides were co-upregulated under the treatment of low temperature, which can alleviate the damages induced by temperature stress and maintain the normal growth and metabolism of algal cells. CONCLUSIONS: X. hormidioides is a psychrotolerant microalga. It is an oleaginous filamentous microalga containing hyper palmitoleic acid and a certain amount of eicosapentaenoic acid with great potential for biofuel development, as well as for applications in nutritional health products and other industries.

MicroRNA-708 prevents ethanol-induced hepatic lipid accumulation and inflammatory reaction via direct targeting ZEB1.

Alcoholic liver disease (ALD) was a global liver disease which divided into liver inflammation, fatty liver, alcoholic hepatitis or cirrhosis. Abnormal expression levels of some microRNAs (miRNA) family members often lead to ALD and other liver diseases. MicroRNA-708 (miR-708) was known to suppress the proliferation and metastasis of hepatocellular carcinoma (HCC), but its role in the progression of ALD was not clear. In this study, the expression level of miR-708 was down-regulated in ethanol-induced L0-2 cells. ZEB1 could decrease the PPAR-α expression while increase the SREBP-1 expression. Meanwhile, the expression levels of TNF-α and IL-6 were up-regulated by ZEB1. Of note, ZEB1 aggravated the apoptotic rate of L0-2 cells induced by ethanol via inhibiting p-AKT and p-mTOR of AKT/mTOR signaling pathway. What's more, it was demonstrated that miR-708 family members particularly target ZEB1 3'-UTR regions and can down-regulate the expression level of ZEB1 in L0-2 cells. Sum up, these results indicated that miR-708 might inhibit the liver inflammation and lipid accumulation by targeting ZEB1 via regulating AKT/mTOR signaling pathway.