OBJECTIVEThe beneficial effects of the inactivation of endocannabinoid system (ECS) by administration of antagonists of the cannabinoid receptor (CB) 1 on several pathological features associated with obesity is well demonstrated, but the relative contribution of central versus peripheral mechanisms is unclear.We examined the impact of CB1 antagonism on liver and adipose tissue lipid metabolism in a mouse model of diet-induced obesity.RESEARCH DESIGN AND METHODSMice were fed either with a standard diet or a high-sucrose high-fat (HSHF) diet for 19 weeks and then treated with the CB1-specific antagonist SR141716 (10 mg · kg−1 · day−1) for 6 weeks.RESULTSTreatment with SR141716 reduced fat mass, insulin levels, and liver triglycerides primarily increased by HSHF feeding. Serum adiponectin levels were restored after being reduced in HSHF mice. Gene expression of scavenger receptor class B type I and hepatic lipase was induced by CB1 blockade and associated with an increase in HDL-cholesteryl ether uptake. Concomitantly, the expression of CB1, which was strongly increased in the liver and adipose tissue of HSHF mice, was totally normalized by the treatment. Interestingly, in visceral but not subcutaneous fat, genes involved in transport, synthesis, oxidation, and release of fatty acids were upregulated by HSHF feeding, while this effect was counteracted by CB1 antagonism.CONCLUSIONSA reduction in the CB1-mediated ECS activity in visceral fat is associated with a normalization of adipocyte metabolism, which may be a determining factor in the reversion of liver steatosis induced by treatment with SR141716.
Herbivorous grass carp (Ctenopharyngodon idella) has been reported to exhibit low capacity to utilize high dietary lipid, but different lipid sources might affect this limited capacity. In order to compare the effects of different lipid sources with different lipid levels, juvenile grass carp were fed one of nine diets containing three oils [lard, plant oil mixed by maize and linseed oil, and n‐3 high unsaturated fatty acid‐enriched (HUFA‐enriched) fish oil] at three lipid levels (20, 60 and 100 g kg−1 dry diet) for 8 weeks. Decreased feed intake, poor growth performance, hepatic pathology and higher blood lipid peroxidation were found in 60 and 100 g kg−1 fish oil groups. Conversely, in lard and plant oil groups, even at 100 g kg−1 dietary lipid level, feed intake and growth performance did not decrease, despite histological observation revealed hepatic pathology in these groups. Plasma triglyceride and cholesterol contents increased significantly in all 100 g kg−1 dietary lipid groups. In the comparison of hepatic FA β‐oxidation among three oil groups at 60 g kg−1 dietary lipid level, impaired mitochondrial and peroxisomal FA oxidation capacity was observed in fish oil group. The results confirmed the relatively low capacity of grass carp to utilize high dietary lipid, and furthermore excess HUFA intake will result in more serious adverse effects than other FA.
The expression of the putative membrane fatty-acid transporter (FAT) was investigated in the small intestine. The FAT mRNA level was higher in the jejunum than in the duodenum and was lower in the ileum, as observed for cytosolic fatty-acid-binding proteins (FABP) expressed in this tissue. No FAT transcript was found in the stomach or colon. FAT mRNA was constitutively expressed i n the epithelial cells located in the upper two thirds of villi, while it was undectectable in the crypt cells and submucosal cells. In jejunal mucosa, immunochemical studies showed that FAT protein was limited to the brush border of enterocytes. No fluorescence was found in the goblet cells. To determine whether FAT responded to changes in fat intake, as reported for FABP, the effect of two high-fat diets, which essentially contained either medium-chain fatty acids or long-chain fatty acids (sunflower-oil diet), was investigated. The sunflower-oil diet greatly increased FAT mRNA abundance throughout the small intestine. In contrast, a weak effect of medium-chain fatty acids was observed only in the jejunum. As found for FABP expression, treatment with the hypolipidemic drug bezafibrate affected FAT expression. These data demonstrate that FAT and FABP are co-expressed in enterocytes, as has been shown in adipocytes, myocytes and mammary cells. The data suggest that these membrane and cytosolic proteins might have complementary functions during dietary-fat absorption.Keywords: fatty-acid transporter ; fatty-acid-binding protein ; small intestine ; gene regulation ; lipid.How long-chain fatty acids (LCFA) move across the biological membranes is subject to controversy. Because of their lipophilic character, they were expected to diffuse freely through the plasma membrane of cells [I]. However, this concept was challenged by the finding of a rapid and saturable uptake, which was reduced by prior heat denaturation or protease treatment of cells 121, and by the isolation and characterization of several plasma-membrane proteins that showed high affinity for LCFA [2-51. The small intestine might express at least two of these proteins: the plasma-membrane fatty-acid-binding protein (FABP) and the fatty-acid transporter (FAT) [6]. The plasmamembrane FABP is a 40-kDa protein postulated to mediate fatty acid uptake through an active sodium-dependent process in the gut 17, 81. The regulation of this protein is unknown since it has not been cloned. FAT is a 88-kDa membrane protein, which was cloned recently in adipocytes, where it might be involved in the sequestration and uptake of fatty acids 191. This protein, which is similar to the CD36 glycoprotein [lo], was detected by means of Northern blot analysis in various tissues including the small intestine [9].Once within the cell, LCFA bind to 14-1 5-kDa cytosolic proteins termed fatty-acid-binding proteins (FABP), which are thought to be involved in facilitation of LCFA desorption from the plasma membrane and diffusion of LCFA through the cytosol [ll]. Several recent reports showed that the express...
The membrane glycoprotein CD36 binds nanomolar concentrations of long chain fatty acids (LCFA) and is highly expressed on the luminal surface of enterocytes. CD36 deficiency reduces chylomicron production through unknown mechanisms. In this report, we provide novel insights into some of the underlying mechanisms. Our in vivo data demonstrate that CD36 gene deletion in mice does not affect LCFA uptake and subsequent esterification into triglycerides by the intestinal mucosa exposed to the micellar LCFA concentrations prevailing in the intestine. In rodents, the CD36 protein disappears early from the luminal side of intestinal villi during the postprandial period, but only when the diet contains lipids. This drop is significant 1 h after a lipid supply and associates with ubiquitination of CD36. Using CHO cells expressing CD36, it is shown that the digestion products LCFA and diglycerides trigger CD36 ubiquitination. In vivo treatment with the proteasome inhibitor MG132 prevents the lipid-mediated degradation of CD36. In vivo and ex vivo, CD36 is shown to be required for lipid activation of ERK1/2, which associates with an increase of the key chylomicron synthesis proteins, apolipoprotein B48 and microsomal triglyceride transfer protein. Therefore, intestinal CD36, possibly through ERK1/2-mediated signaling, is involved in the adaptation of enterocyte metabolism to the postprandial lipid challenge by promoting the production of large triglyceride-rich lipoproteins that are rapidly cleared in the blood. This suggests that CD36 may be a therapeutic target for reducing the postprandial hypertriglyceridemia and associated cardiovascular risks.CD36 (also known as fatty acid translocase) is a transmembrane glycoprotein expressed in many tissues. It is a multifunctional protein homologous to scavenger receptor class B, type I. CD36 facilitates uptake of long chain fatty acids (LCFA) 2 in cardiomyocytes (1) and adipocytes (2, 3) and that of oxidized LDL by macrophages (4). CD36 is involved in platelet aggregation by binding thrombospondin and collagen (5), phagocytosis of apoptotic cells by macrophages (6), and the cytoadhesion of erythrocytes infected with Plasmodium falciparum (7). In addition, CD36 has recently been shown to play a role in taste perception of dietary fatty acid on the tongue by triggering a cell signaling cascade (8 -10). Deletion of CD36 in mice highlighted the importance of this protein for optimal utilization of dietary lipids. Significant impairment in the uptake of LCFA by skeletal muscle, heart, and adipose tissues was shown (2). Insulin-and exercise-dependent translocation of CD36 from an intracellular pool to the sarcolemna was documented and postulated to increase the muscle efficiency by allowing adaptive changes in LCFA uptake and utilization (11, 12). Finally, CD36-deficient mice exhibit a loss of the spontaneous preference for lipid-rich foods and a decrease of orosensory-mediated rise in digestive secretions (8, 9). In humans, variants in the CD36 gene have been associated with abnormalit...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.