补充牛磺酸对正常大鼠脂代谢的影响

为研究不同牛磺酸水平对正常大鼠血脂的影响 ,将 40只断乳SD大鼠用基础饲料喂养一周后 ,按体重和血浆总胆固醇均衡的原则分为 4组 ,对照组进食正常饲料 ,其余 3组分别在基础饲料的基础上添加不同水平 (6、1.35和 3g kg饲料 )的牛磺酸 ;实验 5周后 ,观察牛磺酸对大鼠血脂的影响。结果表明 ,与正常对照组相比 ,不同剂量的牛磺酸均可显著影响大鼠血浆脂质水平 ;6g kg牛磺酸降低血清总胆固醇、低密度脂蛋白胆固醇效果最明显 ,13.5g kg牛磺酸可显著降低血清甘油三酯、载脂蛋白 B水平 ,促进粪胆汁酸排泄 ;30g kg牛磺酸对降低大鼠肝脏总胆固醇、升高血清载脂蛋白效果较好。

Monounsaturated fat decreases hepatic lipid content in non-alcoholic fatty liver disease in rats

AIM： To evaluate the effects of different types of dietary fats on the hepatic lipid content and oxidative stress parameters in rat liver with experimental non-alcoholic fatty liver disease （NAFLD）. METHODS： A total of 32 Sprague-Dawley rats were randomly divided into five groups. The rats in the control group （n = 8） were on chow diet （Group 1）, rats （n = 6） on methionine choline-deficient diet （MCDD） （Group 2）, rats （n = 6） on MCDD enriched with olive oil （Group 3）, rats （n = 6） on MCDD with fish oil （Group 4） and rats （n = 6） on MCDD with butter fat （Group 5）. After 2 mo, blood and liver sections were examined for lipids composition and oxidative stress parameters. RESULTS： The liver weight/rat weight ratio increased in all treatment groups as compared with the control group. Severe fatty liver was seen in MCDD ＋ fish oil and in MCDD ＋ butter fat groups, but not in MCDD and MCDD ＋ olive oil groups. The increase in hepatic triglycerides （TG） levels was blunted by 30% in MCDD ＋ olive oil group （0.59 ±0.09） compared with MCDD group （0.85 ±0.04, P 〈 0.004）, by 37% compared with MCDD ＋ fish oil group （0.95 ±0.07, P 〈 0.001）, and by 33% compared with MCDD ＋ butter group （0.09 ±0.1, P 〈 0.01）. The increase in serum TG was lowered by 10% in MCDD ＋ olive oil group （0.9 ±0.07） compared with MCDD group （1.05 ±0.06）. Hepatic cholesterol increased by 15-fold in MCDD group [（0.08 ±0.02, this increment was blunted by 21% in MCDD ＋ fish oil group （0.09 ±0.02）]. In comparison with the control group, ratio of long-chain polyunsaturated fatty acids omega-6/omega-3 increased in MCDD ＋ olive oil, MCDD ＋ fish oil and MCDD ＋ butter fat groups by 345-, 30- and 397-fold, respectively. In comparison to MCDD group （1.58 ±0.08）, hepatic MDA contents in MCDD ＋ olive oil （3.3 ±0.6）, MCDD ＋ fish oil （3.0 ±0.4）, and MCDD ＋ butter group （2.9 ±0.36） were increased by 108%, 91% and 87%, respectively （P 〈 0.004）. Hepatic paraoxonase activity decreased significantly in all treatment groups, mostly with MCDD ＋ olive oil group （-68%）.CONCLUSION： Olive oil decreases the accumulation of triglyceride in the liver of rats with NAFLD, but does not provide the greatest antioxidant activity.

ATF4 regulates lipid metabolism and thermogenesis

Activating transcription factor 4 （ATF4） has been shown to play key roles in many physiological processes. There are no reports, however, demonstrating a direct link between ATF4 and lipid metabolism. We noticed that Atf4- deficient mice are lean, suggesting a possible role for ATF4 in regulating lipid metabolism. The goal of our current study is to investigate the involvement of ATF4 in lipid metabolism and elucidate the underlying mechanisms. Studies using Atf4-deficient mice revealed increased energy expenditure, as measured by oxygen consumption. These mice also showed increases in lipolysis, expression of uncoupling protein 2 （UCP2） and p-oxidation genes and decreases in expression of lipogenic genes in white adipose tissue （WAT）, suggesting increased utilization and decreased synthesis of fatty acids, respectively. Expression of UCP1, 2 and 3 was also increased in brown adipose tissue （BAT）, suggesting increased thermogenesis. The effect of ATF4 deletion on expression of UCPs in BAT suggests that increased thermogenesis may underlie increased energy expenditure. Thus, our study identifies a possible new function for ATF4 in regulating lipid metabolism and thermogenesis.

Roles of the Lipid Metabolism in Hepatic Stellate Cells Activation

Abstract The lipids present in hepatic stellate cells （HSCs） lipid droplets include retinyl ester, triglyceride, cholesteryl ester, cholesterol, phospholipids and free fatty acids. Activation of HSCs is crucial to the development of fibrosis in liver disease. During activation, HSCs transform into myofibroblasts with concomitant loss of their lipid droplets and production of excessive extracellular matrix. Release of lipid droplets containing retinyl esters and triglyceride is a defining feature of activated HSCs. Accumulating evidence supports the proposal that recovering the accumulation of lipids would inhibit the activation of HSCs. In healthy liver, quiescent HSCs store 80% of total liver retinols and release them depending on the extracellular retinol status. However, in injured liver activated HSCs lose their retinols and produce a considerable amount of extracelhilar matrix, subsequently leading to liver fibrosis. Further findings prove that lipid metabolism of HSCs is closely associated with its activation, yet relationship between activated HSCs and the lipid metabolism has remained mysterious.

Role of cyclooxygenase-2 in lipid metabolism in hepatic stellate cells

Hepatic stellate cells(HSCs) are a kind of adipocytes. In HSCs lipids mainly exist in the form of lipid droplets. They are abundantly found in the cytoplasm and their main constituents are triglycerides. Lipid metabolism in HSCs is closely related to its biological activity, however the mechanism of lipid droplets disappearance after HSC activation is not clearly established yet. Recent research shows that, cyclooxygenase-2 plays an important regulatory role in the lipid metabolism of HSCs. This paper seeks to review the subject based on studies that have been conducted so far to understand the role of cyclooxygenase-2 in the metabolism of lipids in HSCs.

Twists and turns—How we stepped into and had fun in the “boring” lipid field

Compared to proteins and RNAs, functional specificities associated with structural variations in fatty acids and lipids have been greatly underexplored. This review describes how our lab naively started to work on lipids 14 years ago, and how we have gradually overcome obstacles to address some interesting biological questions by combining genetics with biochemical methods on the nematode Caenorhabditis elegans. Our studies have revealed lipid variants and their metabolic pathways, in specific tissues, impact development and behaviors by regulating specific signaling events. The review also discusses the general research approach, style of lab management, and funding mechanisms that have facilitated the frequent research direction changes in the lab, including the journey into the lipid field.