Remodeling Intestinal Microbiota Alleviates Severe Combined Hyperlipidemia-Induced Nonalcoholic Steatohepatitis and Atherosclerosis in LDLR-/- Hamsters.

Combined hyperlipidemia (CHL) manifests as elevated cholesterol and triglycerides, associated with fatty liver and cardiovascular diseases. Emerging evidence underscores the crucial role of the intestinal microbiota in metabolic disorders. However, the potential therapeutic viability of remodeling the intestinal microbiota in CHL remains uncertain. In this study, CHL was induced in low-density lipoprotein receptor-deficient (LDLR-/-) hamsters through an 8-week high-fat and high-cholesterol (HFHC) diet or a 4-month high-cholesterol (HC) diet. Placebo or antibiotics were administered through separate or cohousing approaches. Analysis through 16S rDNA sequencing revealed that intermittent antibiotic treatment and the cohousing approach effectively modulated the gut microbiota community without impacting its overall abundance in LDLR-/- hamsters exhibiting severe CHL. Antibiotic treatment mitigated HFHC diet-induced obesity, hyperglycemia, and hyperlipidemia, enhancing thermogenesis and alleviating nonalcoholic steatohepatitis (NASH), concurrently reducing atherosclerotic lesions in LDLR-/- hamsters. Metabolomic analysis revealed a favorable liver lipid metabolism profile. Increased levels of microbiota-derived metabolites, notably butyrate and glycylglycine, also ameliorated NASH and atherosclerosis in HFHC diet-fed LDLR-/- hamsters. Notably, antibiotics, butyrate, and glycylglycine treatment exhibited protective effects in LDLR-/- hamsters on an HC diet, aligning with outcomes observed in the HFHC diet scenario. Our findings highlight the efficacy of remodeling gut microbiota through antibiotic treatment and cohousing in improving obesity, NASH, and atherosclerosis associated with refractory CHL. Increased levels of beneficial microbiota-derived metabolites suggest a potential avenue for microbiome-mediated therapies in addressing CHL-associated diseases.

Depleting LCAT Aggravates Atherosclerosis in LDLR-deficient Hamster with Reduced LDL-Cholesterol Level.

INTRODUCTION: Lecithin cholesterol acyltransferase (LCAT) plays a crucial role in acyl-esterifying cholesterol in plasma, which is essential for reverse cholesterol transport (RCT). Previous studies indicated that its activity on both α and ß lipoproteins interpret its effects on lipoproteins for many controversial investigations of atherosclerosis. OBJECTIVES: To better understand the relationship between LCAT, diet-induced dyslipidemia and atherosclerosis, we developed a double knockout (LCAT-/-&LDLR-/-, DKO) hamster model to evaluate the specific role of LCAT independent of LDL clearance effects. METHODS: Plasma triglyceride (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), and free cholesterol (FC) levels were measured using biochemical reagent kits. FPLC was performed to analyze the components of lipoproteins. Apolipoprotein content was assessed using western blotting (WB). The hamsters were fed a high cholesterol/high fat diet (HCHFD) to induce atherosclerosis. Oil Red O staining was employed to detect plaque formation. Peritoneal macrophages were studied to investigate the effects of LCAT on cholesterol uptake and efflux. RESULTS: On HCHFD, DKO hamsters exhibited significantly elevated levels of TG and FC, while HDL-C was nearly undetectable without affecting TC levels, as compared to low-density lipoprotein receptor (LDLR)-deficient (LDLR-/-, LKO) hamsters. Lipoprotein profiling revealed a marked increase in plasma chylomicron/very low-density lipoprotein (CM/VLDL) fractions, along with an unexpected reduction in LDL fraction in DKO hamsters. Furthermore, DKO hamsters displayed aggravated atherosclerotic lesions in the aorta, aortic root, and coronary artery relative to LKO hamsters, attributed to a pro-atherogenic lipoprotein profile and impaired cholesterol efflux in macrophages. CONCLUSIONS: Our study demonstrates the beneficial role of LCAT in inhibiting atherosclerotic development and highlights the distinctive lipid metabolism characteristics in hamsters with familial hypercholesterolemia.

Comparison of end-of-life tire treatment technologies: a Chinese case study.

The aim of this paper is to compare different end-of-life tire (ELT) treatment technologies in China from an environmental and economic perspective. Four treatment technologies were evaluated: ambient grinding, devulcanization, pyrolysis and illegal tire oil extraction. Life cycle assessment (LCA) was applied to evaluate the potential environmental impact of each treatment based on the Eco-indicator 99 (Hierarchist approach) method provided by GaBi 4 software. The final result shows that pyrolysis represents the environmentally benign option while illegal tire oil extraction caused the worst damages. For the three legal treatments, although high credit was obtained when considering avoided impacts from recycled materials and energy, they have great impact as to respiratory effects (inorganic) dominantly contributed by energy production stage, which implies that the emphasis on environmental policies related to ELT treatment should shift from the control of emissions from treatment process to the reduction of energy consumption. A simplified comparison of net benefits and total impacts shows that the most eco-effective ELT treatment technology is pyrolysis, followed by dynamic devulcanization and ambient grinding. The illegal tire oil extraction, however, must be prohibited immediately because of its highest environmental pollution and lowest net benefit.