Effects Of Dietary Saturated Fat Research Articles

The association between dietary fats and the incidence risk of cardiovascular outcomes: Tehran Lipid and Glucose Study

BackgroundThe association between dietary fats and the risk of cardiovascular disease (CVD) is under debate. We aimed to determine the potential effects of dietary saturated fats (SFA), mono-unsaturated (MUFA) and poly-unsaturated (PUFA) fatty acids on the occurrence of CVD in an adult Asian population.MethodsThis study was conducted within the framework of the Tehran Lipid and Glucose Study on 2809 CVD-free adults, aged ≥ 19 years. Dietary intakes of fats were estimated using a validated 168-items semi-quantitative food frequency questionnaire, at baseline. Adjusted hazard ratios and 95% confidence intervals of CVD were calculated in tertile categories of dietary fats. The risk of CVD was estimated with multivariable Cox regression for the substitution of total fat or SFA with other macronutrients.ResultsDuring 10.6 years of follow up, the incidence rate of CVD events was 7.1%. Mean (± SD) age of the participants was 39 (± 14) years and 43.9% were men. Total fat, animal and plant sources of fats were not associated with risk of CVD events. No significant associations were found between total SFA, lauric acid, myristic acid, stearic acid, palmitic acid as well as MUFA and PUFA and CVD incidence. Substitutions of total fats or SFA with other macronutrients were not associated with CVD risk.ConclusionsIn this study, no significant associations were found between dietary fats and CVD risk. Considering the emerging body of literature that suggests no association between fats and CVD risk, reconsideration of dietary recommendations regarding low fat diets to prevent CVD, seems to be essential.

Improvement of the omega 3 index of healthy subjects does not alter the effects of dietary saturated fats or n-6PUFA on LDL profiles

Background and AimsDietary fat composition is known to modulate circulating lipid and lipoprotein levels. Although supplementation with long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) has been shown to reduce plasma triglyceride levels, the effect of the interactions between LCn-3PUFA and the major dietary fats consumed has not been previously investigated. MethodsIn a randomized controlled parallel design clinical intervention, we examined the effect of diets rich in either saturated fatty acids (SFA) or omega-6 polyunsaturated fatty acids (n-6PUFA) on plasma lipid levels and lipoprotein profiles (lipoprotein size, concentration and distribution in subclasses) in subjects with an adequate omega 3 index. Twenty six healthy subjects went through a four-week pre-supplementation period with LCn-3PUFA and were then randomized to diets rich in either n-6PUFA or SFA both supplemented with LCn-3PUFA. ResultsThe diet rich in n-6PUFA decreased low density lipoprotein (LDL) particle concentration (−8%, p=0.013) and LDL cholesterol (LDL-C) level (−8%, p=0.021), while the saturated fat rich diet did not affect LDL particle concentration or LDL-C levels significantly. Nevertheless, dietary saturated fatty acids increased LCn-3PUFA in plasma and tissue lipids compared with n-6PUFA, potentially reducing other cardiovascular risk factors such as inflammation and clotting tendency. ConclusionImprovement on the omega 3 index of healthy subjects did not alter the known effects of dietary saturated fats and n-6PUFA on LDL profiles.

Alcoholic Liver Disease: Update on the Role of Dietary Fat.

Alcoholic liver disease (ALD) spans a spectrum of liver pathology, including fatty liver, alcoholic steatohepatitis, and cirrhosis. Accumulating evidence suggests that dietary factors, including dietary fat, as well as alcohol, play critical roles in the pathogenesis of ALD. The protective effects of dietary saturated fat (SF) and deleterious effects of dietary unsaturated fat (USF) on alcohol-induced liver pathology are well recognized and documented in experimental animal models of ALD. Moreover, it has been demonstrated in an epidemiological study of alcoholic cirrhosis that dietary intake of SF was associated with a lower mortality rates, whereas dietary intake of USF was associated with a higher mortality. In addition, oxidized lipids (dietary and in vivo generated) may play a role in liver pathology. The understanding of how dietary fat contributes to the ALD pathogenesis will enhance our knowledge regarding the molecular mechanisms of ALD development and progression, and may result in the development of novel diet-based therapeutic strategies for ALD management. This review explores the relevant scientific literature and provides a current understanding of recent advances regarding the role of dietary lipids in ALD pathogenesis.

Effects of dietary fat saturation on fatty acid composition and gene transcription in different tissues of Iberian pigs

The effect of two diets, respectively enriched with SFA (S) and PUFA (P), on FA tissue composition and gene expression was studied in fattened Iberian pigs. The FA composition of adipose, muscular and liver tissues was affected by dietary treatment. S group showed higher MUFA and MUFA/SFA ratio and lower PUFA and n−6/n−3 ratio than P group in all analyzed tissues. In muscle and liver the extracted lipids were separated into neutral lipids and polar lipid fractions which showed significantly different responses to the dietary treatment, especially in liver where no significant effect of diet was observed in NL fraction. The expression of six candidate genes related to lipogenesis and FA oxidation was analyzed by qPCR. In liver, stearoyl CoA desaturase (SCD), acetyl CoA carboxylase alpha (ACACA) and malic enzyme 1 (ME1) genes showed higher expression in S group. SCD, ACACA, ME1, and fatty acid synthase (FASN) gene expression levels showed a wide variation across the tested tissues, with much higher expression levels observed in adipose tissue than other tissues. Tissue FA profile and gene expression results support the deposition of dietary FA, the lipogenic effect of dietary saturated fat in liver and the employment of saturated dietary fat for endogenous synthesis of MUFA in all the analyzed tissues.

Do impaired memory and body weight regulation originate in childhood with diet-induced hippocampal dysfunction?

Do impaired memory and body weight regulation originate in childhood with diet-induced hippocampal dysfunction?

A Role for Peroxisome Proliferator-activated Receptor γ Coactivator 1 (PGC-1) in the Regulation of Cardiac Mitochondrial Phospholipid Biosynthesis

The energy demands of the adult mammalian heart are met largely by ATP generated via oxidation of fatty acids in a high capacity mitochondrial system. Peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1)-α and -β serve as inducible transcriptional coregulators of genes involved in mitochondrial biogenesis and metabolism. Whether PGC-1 plays a role in the regulation of mitochondrial structure is unknown. In this study, mice with combined deficiency of PGC-1α and PGC-1β (PGC-1αβ(-/-)) in adult heart were analyzed. PGC-1αβ(-/-) hearts exhibited a distinctive mitochondrial cristae-stacking abnormality suggestive of a phospholipid abnormality as has been described in humans with genetic defects in cardiolipin (CL) synthesis (Barth syndrome). A subset of molecular species, containing n-3 polyunsaturated species in the CL, phosphatidylcholine, and phosphatidylethanolamine profiles, was reduced in PGC-1αβ-deficient hearts. Gene expression profiling of PGC-1αβ(-/-) hearts revealed reduced expression of the gene encoding CDP-diacylglycerol synthase 1 (Cds1), an enzyme that catalyzes the proximal step in CL biosynthesis. Cds1 gene promoter-reporter cotransfection experiments and chromatin immunoprecipitation studies demonstrated that PGC-1α coregulates estrogen-related receptors to activate the transcription of the Cds1 gene. We conclude that the PGC-1/estrogen-related receptor axis coordinately regulates metabolic and membrane structural programs relevant to the maintenance of high capacity mitochondrial function in heart.

The effects of dietary saturated fat on basal hypothalamic neuroinflammation in rats

Recent evidence has demonstrated that consumption of high fat diets can trigger brain inflammation and subsequent injury in the absence of any peripheral inflammatory signaling. Here we sought to investigate whether a link exists between the concentration of highly saturated fats in the diet and the development of inflammation in the brain of rats and, whether the source of the saturated fat was an important factor in this process. Adult male rats had access to diets with a moderate level of total fat (32% of calories as fat) varying in level of saturated fat [low (20%) vs high (>60%)] and its source (butter or coconut oil). After 8 weeks of diet exposure peripheral and central tissues were collected for analysis of inflammatory signals. Neither blood nor white adipose tissue exhibited any changes in inflammatory mediators regardless of the saturated fat content or the source. In the brain however, we observed significant hypothalamic upregulation of the expression of markers of glial activation as well as of interleukin (IL)-1,6 and nuclear factor (NF)-IL-6, which were highest in the group fed the butter-based diets. The increase in these inflammatory mediators had no effect on basal body temperature or the temperature response to systemic lipopolysaccharide (LPS). The present results indicate that hypothalamic inflammation associated with consumption of diets high in fat is directly linked to the saturated fat content as well as the source of that fat. These effects are likely linked to other pathophysiological changes in the regulation of metabolism.

Effects of dietary saturated fat on LDL subclasses and apolipoprotein CIII in men

Background/ObjectivesSmall dense LDL particles and apolipoprotein (apo) CIII are risk factors for cardiovascular disease (CVD) that can be modulated by diet, but there is little information regarding the effects of dietary saturated fat on their plasma levels. We tested the effects of high vs. low saturated fat intake in the context of a high beef protein diet on levels and composition of LDL subclasses and on apoCIII levels in plasma and LDL.Subjects/MethodsFollowing consumption of a baseline diet (50% CHO, 13% protein, 38% total fat, 15% saturated fat) for 3 wk, 14 healthy men were randomly assigned to two reduced carbohydrate high beef protein diets (31% CHO, 31% protein, 38% fat) that differed in saturated fat content (15% vs. 8%) for 3 wk each in a crossover design.ResultsThe high saturated fat diet resulted in higher mass concentrations of buoyant LDL I, medium density LDL II and dense LDL III, but not the very dense LDL IV; and significant increases in plasma and LDL apoCIII concentration of 9.4% and 33.5%, respectively. The saturated fat-induced changes in LDL apoCIII were specifically correlated with changes in apoCIII content of LDL IV.ConclusionsTaken together with previous observations, these findings suggest that, at least in the context of a lower carbohydrate high beef protein diet, high saturated fat intake may increase CVD risk by metabolic processes that involve apoCIII.

Fad Diets in the Treatment of Diabetes

Use of the term "fad diet" reflects the contentious nature of the debate in the treatment of diabetes and generally targets diets based on carbohydrate restriction, the major challenge to traditional dietary therapy. Although standard low-fat diets more accurately conform to the idea of a practice supported by social pressure rather than scientific data, it is suggested that we might want to give up altogether unscientific terms like "fad" and "healthy." Far from faddish, diets based on carbohydrate restriction have been the historical treatment for diabetes and are still supported by basic biochemistry, and it is argued that they should be considered the "default" diet, the one to try first, in diseases of carbohydrate intolerance or insulin resistance. The barrier to acceptance of low-carbohydrate diets in the past has been concern about saturated fat, which might be substituted for the carbohydrate that is removed. However, recent re-analysis of much old data shows that replacing carbohydrate with saturated fat is, if anything, beneficial. The dialectic of impact of continued hemoglobin A(1c) versus effect of dietary saturated fat in the risk of cardiovascular disease is resolved in direction of glycemic control. Putting biased language behind us and facing the impact of recent results that point to the value of low-carbohydrate diets would offer patients the maximum number of options.

Limited Effect of Dietary Saturated Fat on Plasma Saturated Fat in the Context of a Low Carbohydrate Diet

We recently showed that a hypocaloric carbohydrate restricted diet (CRD) had two striking effects: (1) a reduction in plasma saturated fatty acids (SFA) despite higher intake than a low fat diet, and (2) a decrease in inflammation despite a significant increase in arachidonic acid (ARA). Here we extend these findings in 8 weight stable men who were fed two 6-week CRD (12%en carbohydrate) varying in quality of fat. One CRD emphasized SFA (CRD-SFA, 86 g/d SFA) and the other, unsaturated fat (CRD-UFA, 47 g SFA/d). All foods were provided to subjects. Both CRD decreased serum triacylglycerol (TAG) and insulin, and increased LDL-C particle size. The CRD-UFA significantly decreased plasma TAG SFA (27.48 ± 2.89 mol%) compared to baseline (31.06 ± 4.26 mol%). Plasma TAG SFA, however, remained unchanged in the CRD-SFA (33.14 ± 3.49 mol%) despite a doubling in SFA intake. Both CRD significantly reduced plasma palmitoleic acid (16:1n-7) indicating decreased de novo lipogenesis. CRD-SFA significantly increased plasma phospholipid ARA content, while CRD-UFA significantly increased EPA and DHA. Urine 8-iso PGF2α, a free radical-catalyzed product of ARA, was significantly lower than baseline following CRD-UFA (−32%). There was a significant inverse correlation between changes in urine 8-iso PGF2α and PL ARA on both CRD (r = −0.82 CRD-SFA; r = −0.62 CRD-UFA). These findings are consistent with the concept that dietary saturated fat is efficiently metabolized in the presence of low carbohydrate, and that a CRD results in better preservation of plasma ARA.

Angptl4 Protects Against Severe Pro-Inflammatory Effects of Dietary Saturated Fat by Inhibiting LPL-Dependent Uptake of Fatty Acids in Mesenteric Lymph Node Macrophages

Angptl4 Protects Against Severe Pro-Inflammatory Effects of Dietary Saturated Fat by Inhibiting LPL-Dependent Uptake of Fatty Acids in Mesenteric Lymph Node Macrophages

Saturated fat, carbohydrate, and cardiovascular disease

A focus of dietary recommendations for cardiovascular disease (CVD) prevention and treatment has been a reduction in saturated fat intake, primarily as a means of lowering LDL-cholesterol concentrations. However, the evidence that supports a reduction in saturated fat intake must be evaluated in the context of replacement by other macronutrients. Clinical trials that replaced saturated fat with polyunsaturated fat have generally shown a reduction in CVD events, although several studies showed no effects. An independent association of saturated fat intake with CVD risk has not been consistently shown in prospective epidemiologic studies, although some have provided evidence of an increased risk in young individuals and in women. Replacement of saturated fat by polyunsaturated or monounsaturated fat lowers both LDL and HDL cholesterol. However, replacement with a higher carbohydrate intake, particularly refined carbohydrate, can exacerbate the atherogenic dyslipidemia associated with insulin resistance and obesity that includes increased triglycerides, small LDL particles, and reduced HDL cholesterol. In summary, although substitution of dietary polyunsaturated fat for saturated fat has been shown to lower CVD risk, there are few epidemiologic or clinical trial data to support a benefit of replacing saturated fat with carbohydrate. Furthermore, particularly given the differential effects of dietary saturated fats and carbohydrates on concentrations of larger and smaller LDL particles, respectively, dietary efforts to improve the increasing burden of CVD risk associated with atherogenic dyslipidemia should primarily emphasize the limitation of refined carbohydrate intakes and a reduction in excess adiposity.

The influence of triacylglycerol structure on the oxidative stability of polyunsaturated oils

AbstractThere is a growing trend in the use of unsaturated oils in food products and applications. This stems from mounting scientific evidence and increasing consumer awareness of detrimental health effects of dietary saturated fats and trans fats. A major problem with unsaturated oils is that they oxidise very readily forming compounds that impart off‐flavours to food. Susceptibility of oils to oxidation is often discussed in terms of the degree of unsaturation in the component fatty acids. However, the way in which the unsaturated fatty acids are located within the triacylglycerol molecules (positional distribution) can also influence oxidative stability. This paper reviews the literature on the subject.

(n-3) Long Chain PUFA Dose-Dependently Increase Oxygen Utilization Efficiency and Inhibit Arrhythmias after Saturated Fat Feeding in Rats

Fish oil (FO) modifies cardiac membrane phospholipid fatty acid composition to confer increased efficiency of oxygen utilization and antiarrhythmic effects. We tested the capacity of low-dose increments of FO, rich in (n-3) PUFA, to reverse the detrimental pro-arrhythmic and inefficient oxygen usage effects of dietary saturated fat (SAT) [including high ratio of (n-6) PUFA:(n-3) PUFA] during ischemia and reperfusion. Wistar rats were fed an SAT-enriched diet (15.3% fat, including 12% SAT, added by weight) for 6 wk and were then divided into 4 groups (n = 10/group) fed that diet or a 12% fat diet containing 3, 6, or 12% FO in place of SAT for 6 wk. Paced (300/min), erythrocyte-perfused isolated working hearts were subjected to low coronary flow ischemia (15 min) and were then reperfused. At normoxic baseline, external work capacity increased marginally at 6 and 12% FO; however, marked dose-related reductions in oxygen consumption were evident due to FO-dependent reduction in oxygen-energy utilization efficiency and associated reductions in coronary flow and oxygen extraction. Postischemic recovery resulted in lower oxygen consumption, greater oxygen-energy utilization efficiency, reduced coronary release of creatine kinase, and reduced incidence of arrhythmias in all FO groups compared with the SAT group. FO at a dose as low as 3% of total fat dietary supplement effectively reversed the high oxygen requirements and pro-arrhythmic effects of a SAT-rich diet even with continued consumption of SAT (9%) in this ex vivo animal model.

Lipodystrophic and Lipo-Peroxidative Effects of Hydrogenated Coconut Oil Diet in Rats

2 Abstract: The effects of dietary saturated fat on blood lipid and lipoprotein composition and lipid peroxidation were studied in rats. Male albino rats (Rattus norvegicus) were maintained either on diets with 5% fa t supplements made of 5% soyabean oil or 5% coconut oil. Similarly, two other groups were fed diets that were isocaloric with the former but contained 25% fat supplements made of 25% soyabean oil or 25 % coconut oil. The concentration of triacylglycerols in the plasma of the high coconut oil fed rats was three to six-times those of the others. The concentration of free cholesterol was much higher in the plasma of the coconut oil-fed rats. There were significant decreases in the plasma level of chylomirons, VLDL and HDL, but a significant increase in the LDL level of the coconut oil-fed rats. In all the tissues studied, the malondialdehyde level increased significantly in the coconut oil fed rats and most prominently in the liver and the kidney, while the reduced glutathione levels decreased significantly in the coconut oil-fed rats. It i s considered that ingestion of coconut oil for a considerably long time may affect lipid metabolism and alter the structure and function of the enzymes responsible for converting the essential fatty acids to prostaglandins or their endoperoxide precursors. The increase in the malondialdehyde level and the decrease in the reduced glutathione level are indications of the lipid peroxidative effect of saturated fat diet, while the reduced HDL and high level of LDL can be major contributory factors to atherogenesis.

Stearoyl CoA desaturase‐1 mediates the pro‐lipogenic effects of dietary saturated fat

Dietary saturated fats have often been implicated in the promotion of obesity and related disorders. It has been shown recently that saturated fats act through the transcription factor SREBP-1c (sterol regulatory element-binding protein-1c) and its requisite coactivator, peroxisome proliferator-activated receptor-γ coactivator-1β (PGC-1β), to exert their pro-lipogenic effects. We show here that a diet high in the saturated fat stearate induces lipogenic genes in wild-type mice, with the induction of the Scd1 (stearoyl-CoA desaturase-1) gene preceding that of other lipogenic genes. However, in Scd1-/- mice, stearate does not induce lipogenesis, and Srebp-1c and Pgc-1β levels are markedly reduced. Instead, genes of fatty acid oxidation such as Cpt-1 (carnitine palmitoyltransferase-1) as well as Pgc-1α are induced. Mitochondrial fatty acid oxidation is increased, and white adipose tissue and hepatic glycogen stores are depleted in stearate-fed Scd1-/- mice. Furthermore, AMP-activated protein kinase is also induced by stearate feeding in Scd1-/- mice. These results indicate that the desaturation of saturated fats such as stearate by SCD is an essential step mediating their induction of lipogenesis. In the absence of SCD1, stearate promotes oxidation, leading to protection from saturated fat-induced obesity. SCD1 thus serves as a molecular switch in the promotion or prevention of lipid-induced disorders brought on by consumption of excess saturated fat.

Stearoyl-CoA Desaturase-1 Mediates the Pro-lipogenic Effects of Dietary Saturated Fat

Dietary saturated fats have often been implicated in the promotion of obesity and related disorders. It has been shown recently that saturated fats act through the transcription factor SREBP-1c (sterol regulatory element-binding protein-1c) and its requisite coactivator, peroxisome proliferator-activated receptor-gamma coactivator-1beta (PGC-1beta), to exert their pro-lipogenic effects. We show here that a diet high in the saturated fat stearate induces lipogenic genes in wild-type mice, with the induction of the Scd1 (stearoyl-CoA desaturase-1) gene preceding that of other lipogenic genes. However, in Scd1-/- mice, stearate does not induce lipogenesis, and Srebp-1c and Pgc-1beta levels are markedly reduced. Instead, genes of fatty acid oxidation such as Cpt-1 (carnitine palmitoyltransferase-1) as well as Pgc-1alpha are induced. Mitochondrial fatty acid oxidation is increased, and white adipose tissue and hepatic glycogen stores are depleted in stearate-fed Scd1-/- mice. Furthermore, AMP-activated protein kinase is also induced by stearate feeding in Scd1-/- mice. These results indicate that the desaturation of saturated fats such as stearate by SCD is an essential step mediating their induction of lipogenesis. In the absence of SCD1, stearate promotes oxidation, leading to protection from saturated fat-induced obesity. SCD1 thus serves as a molecular switch in the promotion or prevention of lipid-induced disorders brought on by consumption of excess saturated fat.

The Transcriptional Coactivator PGC-1β Drives the Formation of Oxidative Type IIX Fibers in Skeletal Muscle

Skeletal muscle must perform different kinds of work, and distinct fiber types have evolved to accommodate these. Previous work had shown that the transcriptional coactivator PGC-1alpha drives the formation of type I and IIA muscle fibers, which are "slow-twitch" and highly oxidative. We show here that transgenic expression of PGC-1beta, a coactivator functionally similar to but distinct from PGC-1alpha, causes a marked induction of IIX fibers, which are oxidative but have "fast-twitch" biophysical properties. PGC-1beta coactivates the MEF2 family of transcription factors to stimulate the type IIX myosin heavy chain (MHC) promoter. PGC-1beta transgenic muscle fibers are rich in mitochondria and are highly oxidative, at least in part due to coactivation by PGC-1beta of ERRalpha and PPARalpha. Consequently, these transgenic animals can run for longer and at higher work loads than wild-type animals. Together, these data indicate that PGC-1beta drives the formation of highly oxidative fibers containing type IIX MHC.

PPARα activation reverses adverse effects induced by high-saturated-fat feeding on pancreatic β-cell function in late pregnancy

We examined whether the additional demand for insulin secretion imposed by dietary saturated fat-induced insulin resistance during pregnancy is accommodated at late pregnancy, already characterized by insulin resistance. We also assessed whether effects of dietary saturated fat are influenced by PPARalpha activation or substitution of 7% of dietary fatty acids (FAs) with long-chain omega-3 FA, manipulations that improve insulin action in the nonpregnant state. Glucose tolerance at day 19 of pregnancy in the rat was impaired by high-saturated-fat feeding throughout pregnancy. Despite modestly enhanced glucose-stimulated insulin secretion (GSIS) in vivo, islet perifusions revealed an increased glucose threshold and decreased glucose responsiveness of GSIS in the saturated-fat-fed pregnant group. Thus, insulin resistance evoked by dietary saturated fat is partially countered by augmented insulin secretion, but compensation is compromised by impaired islet function. Substitution of 7% of saturated FA with long-chain omega-3 FA suppressed GSIS in vivo but did not modify the effect of saturated-fat feeding to impair GSIS by perifused islets. PPARalpha activation (24 h) rescued impaired islet function that was identified using perifused islets, but GSIS in vivo was suppressed such that glucose tolerance was not improved, suggesting modification of the feedback loop between insulin action and secretion.

Trans geometric isomers of EPA decrease LXRα-induced cellular triacylglycerol via suppression of SREBP-1c and PGC-1β

Dietary mono- or di-trans fatty acids with chain lengths of 18-22 increase the risk of cardiovascular diseases because they increase LDL cholesterol and decrease HDL cholesterol in the plasma. However, the effects of trans isomers of PUFAs on lipid metabolism remain unknown. Dietary PUFAs, especially eicosapentaenoic acid (EPA) in marine oils, improve serum lipid profiles by suppressing liver X receptor alpha (LXRalpha) activity in the liver. In this study, we compared the effects of trans geometric isomers of eicosapentaenoic acid (TEPA) on triacylglycerol synthesis induced by a synthetic LXRalpha agonist (T0901317) with the effects of EPA in HepG2 cells. TEPA significantly decreased the amount of cellular triacylglycerol and the expression of mRNAs encoding fatty acid synthase, stearoyl-CoA desaturase-1, and glycerol-3-phosphate acyltransferase induced by T0901317 compared with EPA. However, there was no significant difference between the suppressive effect of TEPA or EPA on the expression of sterol-regulatory element binding protein-1c (SREBP-1c) induced by T0901317. We found that TEPA, but not EPA, decreased the mRNA expression of peroxisome proliferator-activated receptor gamma coactivator 1beta (PGC-1beta), which is a coactivator of both LXRalpha and SREBP-1. These results suggest that the hypolipidemic effect of TEPA can be attributed to a decrease not only in SREBP-1 but also in PGC-1beta expression.