Selective mobilisation of fatty acids from human adipose tissue

Background: Adipose tissue is a storage organ for dietary fat. During fasting, fatty acids are released into serum as free fatty acids (FFA). Experimental studies indicate that fatty acids are selectively mobilised from adipose tissue into serum. The aim of this study was to investigate whether the composition of the serum FFA fraction reflects selective mobilisation in the fasting state in humans. Methods: The fatty acid composition of fasting serum FFA and adipose tissue were analysed from 112 patients with myocardial infarction and 107 healthy control subjects using gas-liquid chromatography. The subjects' habitual diet was analysed using a food-frequency questionnaire. Results: Significant correlations were found between serum FFA and adipose tissue, particularly for the percentage content of linoleic acid (r=0.73), eicosapentaenoic acid (r=0.68), alpha-linolenic acid (r=0.67) and palmitoleic acid (r=0.60). Percentage contents of palmitic, stearic, linoleic, alpha-linolenic, eicosapentaenoic and docosahexaenoic acid were higher in serum FFA than in adipose tissue, whereas oleic and palmitoleic acid were relatively more abundant in adipose tissue. This may indicate that the former group of fatty acids is preferentially mobilised from adipose tissue into serum. High correlations for polyunsaturated fatty acids were observed between percentage contents of dietary and adipose tissue fatty acids. The correlation of fatty acids between diet and serum FFA was weak, but a tendency towards higher correlations for polyunsaturated fatty acids was observed. Conclusions: Our findings are compatible with the hypothesis that, in the fasting state, fatty acids are selectively mobilised from adipose tissue into serum FFA.     

Fatty acid composition of liver triglycerides in various stages of fat deposition in the parenchyma

Summary In 30 diabetic inpatients the fatty acid pattern of triglycerides in parenchymal liver cells was studied by gas-liquid chromatography. With increasing size of fat droplets, a significant increase in the proportion of palmitic and oleic acid was observed as well as a significant fall of arachidonic (C 20: 4) and eicosapentaenoic acid (C 20: 5).     

Fatty acid composition in serum lipids and adipose tissue in severe obesity before and after six weeks of weight loss

Fatty acid composition was studied in 25 grossly obese patients (mean weight 116 +/- 21 (s.d.) kg) before and after 6 weeks of treatment with a combined program consisting of diet, behavioral modification and light exercise. Data were compared with results from nonobese controls. In obese patients the most marked differences were reduced relative contents of linoleic acid in serum triglycerides (P less than 0.001), cholesterol esters (P less than 0.05) and phospholipids (P less than 0.001). Linolenic acid was reduced in serum triglycerides (P less than 0.001) and in cholesterol esters (P less than 0.01). There were reciprocal increases in palmitic and palmitoleic acid (P less than 0.05) in these two serum lipid fractions. In adipose tissue of obese patients only minor differences were found in palmitoleic acid, which was increased, and in the saturated fatty acids with 14, 16 and 18 carbon atoms which were decreased. Weight loss (600 kcal/day for 6 weeks, P/S ratio about 0.5) did not affect adipose tissue fatty acid composition, but resulted in reductions of linoleic acid content in cholesterol esters and phospholipids, with reciprocal increases of palmitic and arachidonic acid in these fractions. Our results suggest that obese patients have low essential fatty acids content in their circulating plasma lipids already in a weight stable phase. Therefore it may be argued that in the development of long-term dietary restriction programs attention should be paid to the quality of the dietary fat.     

Fatty acid metabolism in primary hyperlipoproteinemia (HLP) (author's transl)

The fatty acid spectra of cholesterol ester and triglyceride fractions separated by thin-layer chromatography were analyzed by gas chromatography in the sera of 252 patients with primary HLP (with 53 cases of type IIa, 48 cases of type IIb, and 151 cases of type IV) and 60 healthy persons. Showing significantly increased values in the cholesterol ester fraction for HLP of types IIa and IIb as well as in the triglyceride fraction for HLP of types IIb and IV were palmitic acid, stearic acid, palmitoleic acid, oleic acid, and eicosatrienic acid. Significantly reduced percentages were obtained for linoleic acid, linolenic acid, arachidonic acid, and eicosapentaenic acid in the same fractions for these types. Possible causes include disturbances of the fatty acid metabolism in the liver, increased selective reesterification of fatty acids of the lipolytic process, and partially altered LCAT activity.     

Improvement of diabetic control by continuous subcutaneous insulin infusion therapy changes fatty acid composition of serum lipids and erythrocytes in Type 1 (insulin-dependent) diabetes

Summary The influence of improved diabetic control on the fatty composition of serum lipids, erythrocytes and platelets was investigated in 24 patients with Type 1 (insulin-dependent) diabetes treated for 6 months with either continuous subcutaneous insulin infusion (n = 14) or conventional insulin therapy (n = 10). The groups were matched for age, sex, body mass index, serum lipids, duration of diabetes, glycosylated haemoglobin and insulin dose. Glycaemic control improved, and the contents of dihomogammalinolenic acid and arachidonic acid but not linoleic acid rose significantly (p < 0.05), in serum lipids of patients treated with continuous infusion. No changes were observed in the group treated with insulin injections. Both in serum and erythrocytes the n-6 polyunsaturated fatty acid ratios rose consistently in the patients, with improvement of control regardless of the mode of treatment. Furthermore, the change of HbA₁ was negatively correlated with that of arachidonic acid in erythrocytes. No changes were found in the platelet fatty acid compositions. The findings suggest that improved diabetic control enhances the conversion of linoleic acid to arachidonic acid, probably by activating enzymes needed for chain elongation and desaturation.     

Contrasting effects of low or high copper intake on rat tissue lipid essential fatty acid composition

The effects of low copper intake or copper supplementation on the metabolism of stearic acid have been studied previously, but their effects on essential fatty acids have not been reported. Male Sprague-Dawley rats were fed for 12 weeks on pelleted semi-synthetic diets containing less than 1 mg/kg copper (low copper), 6 mg/kg (copper control), or 250 mg/kg copper (copper supplemented). The fatty acid composition of the total phopholipids and triglycerides of plasma, liver, heart and adipose tissue was analyzed by gas liquid chromatography. In low copper rats compared to controls, palmitic and oleic acids were decreased but stearic acid and docosahexaenoic acid were increased in plasma, liver and heart phopholipids. Arachidonic acid was also increased in plasma and liver phospholipids in low copper rats. In liver triglycerides, linoleic and arachidonic acids were increased but palmitic and oleic acid were decreased in low copper rats. Copper supplementation had the opposite effect; palmitic and oleic acids were increased in phospholipids and triglycerides whereas essential fatty acids were generally decreased. Hence, copper not only has a direct effect on the desaturation of stearic acid but also has significant effects on the tissue lipid composition of essential fatty acids.     

Roles of adipose restriction and metabolic factors in progression of steatosis to steatohepatitis in obese, diabetic mice

Background and Aims: We previously reported that steatohepatitis develops in obese, hypercholesterolemic, diabetic foz/foz mice fed a high‐fat (HF) diet for 12 months. We now report earlier onset of steatohepatitis in relation to metabolic abnormalities, and clarify the roles of dietary fat and bodily lipid partitioning on steatosis severity, liver injury and inflammatory recruitment in this novel non‐alcoholic steatohepatitis (NASH) model. Methods: Foz/foz (Alms1 mutant) and wild‐type (WT) mice were fed a HF diet or chow, and metabolic characteristics and liver histology were studied at 2, 6, 12 and 24 weeks. Results: After 12 weeks HF‐feeding, foz/foz mice were obese and diabetic with approximately 70% reduction in serum adiponectin. Hepatomegaly developed at this time, corresponding to a plateau in adipose expansion and increased adipose inflammation. Liver histology showed mild inflammation and hepatocyte ballooning as well as steatosis. By 24 weeks, HF‐fed foz/foz mice developed severe steatohepatitis (marked steatosis, alanine aminotransferase elevation, ballooning, inflammation, fibrosis), whereas dietary and genetic controls showed only simple steatosis. While steatosis was associated with hepatic lipogenesis, indicated by increased fatty acid synthase activity, steatohepatitis was associated with significantly higher levels of CD36, indicating active fatty acid uptake, possibly under the influence of peroxisome proliferator‐activated receptor‐γ. Conclusion: In mice genetically predisposed to obesity and diabetes, HF feeding leads to restriction of adipose tissue for accommodation of excess energy, causing lipid partitioning into liver, and transformation of simple steatosis to fibrosing steatohepatitis. The way in which HF feeding ‘saturates’ adipose stores, decreases serum adiponectin and causes hepatic inflammation in steatohepatitis may provide clues to pathogenesis of NASH in metabolic syndrome.     

Physical training and adipose tissue fatty acid composition in men

Four months physical training significantly raised the mean proportions (%) of lauric (+0.64), myristic (+0.52), stearic (+2.06) and linoleic (+1.69) acids and lowered the mean proportions of palmitic (?1.46) and oleic (?3.46) acids in adipose tissue of 20 apparently normal men aged 20–55 yr. These changes were dependent on pretraining proportions of the fatty acids. In addition, the decreases in palmitic acid and oleic acid proportions were positively correlated (? = 0.905, P < 0.01, τ = 0.758, P < 0.01). The pattern of significant correlations among adipose tissue fatty acids was altered as a result of training. We suggest that preferential mobilisation of fatty acids from adipose tissue is responsible for the change in adipose tissue fatty acid composition with increased physical training. The significant increase in adipose tissue linoleic acid proportions may be linked with the reduced risk of coronary heart disease which has been previously associated with increased physical activity.     

Pronounced lipoprotein lipid reduction obtained by combined lipid-lowering treatment in patients with atherosclerotic disease.

The feasibility of reducing serum lipoprotein levels in patients with atherosclerotic disease by combining diet, clofibrate and nicotinic acid (niceritrol) has been investigated. An additive lipid-lowering effect of diet and the two drugs was demonstrated. It was possible to reduce the serum triglycerides (TG) in hypertriglyceridaemic patients by 50-60%. This corresponded to a reduction of very low density lipoprotein (VLDL) TG by 73 and 66% in patients with hyperlipoproteinaemia (HLP) type IIB and IV, respectively. In normotriglyceridaemic patients the serum TG concentration decreased by 30-40%. The serum cholesterol (Chol) concentration was reduced by 33% and the low density lipoprotein (LDL) Chol by 37% in HLP type IIA and IIB. The LDL Chol decreased by 32% in normolipoproteinaemic patients and by 21% in HLP type IV. The mean value for serum cholesterol after therapy was in all groups close to 200 mg/100 ml. In hypertriglyceridaemic patients high density lipoprotein (HDL) Chol increased by 18%. Clofibrate and niceritrol differed with regard to the effect on serum lipoprotein concentrations as well as on other metabolic parameters. Niceritrol was significantly more effective than clofibrate in lowering LDL Chol and in increasing HDL Chol. Niceritrol treatment significantly reduced the Chol/TG ratio in VLDL while no such effect was seen during clofibrate administration. The two drugs also showed significantly different effects on the fractional removal rate (K2) of triglyceride-rich lipoproteins as measured by the intravenous fat tolerance test (IVFTT). The K2 was significantly increased by clofibrate but was not affected by niceritrol treatment. The two drugs differed also with regard to the effects on serum uric acid concentration and the liver function tests. The plasma fibrinogen levels and the erythrocyte sedimentation rates were reduced during treatment with both niceritrol and clofibrate. The present study demonstrates that it is possible to obtain substantial reductions of serum lipoprotein concentrations by combining lipid-lowering diet, clofibrate and niceritrol treatment. There was an additive lipid-lowering effect of this treatment and the combination of the two drugs seemed beneficial in regard to certain possible side effects. The impact of a lipid reduction within this range on cardiovascular morbidity and mortality remains to be evaluated.     

High-fat diet-induced hyperglycemia and obesity in mice: Differential effects of dietary oils

Mice fed a high-fat diet develop hyperglycemia and obesity. Using non-insulin-dependent diabetes mellitus (NIDDM) model mice, we investigated the effects of seven different dietary oils on glucose metabolism: palm oil, which contains mainly 45% palmitic acid (16:0) and 40% oleic acid (18:1); lard oil, 24% palmitic and 44% oleic acid; rapeseed oil, 59% oleic and 20% linoleic acid (18:2); soybean oil, 24% oleic and 54% linoleic acid; safflower oil, 76% linoleic acid; perilla oil, 58% α-linolenic acid; and tuna fish oil, 7% eicosapentaenoic acid and 23% docosahexaenoic acid. C57BL/6J mice received each as a high-fat diet (60% of total calories) for 19 weeks (n = 6 to 11 per group). After 19 weeks of feeding, body weight induced by the diets was in the following order: soybean> palm ≥ lard ≥ rapeseed ≥ safflower ≥ perilla> fish oil. Glucose levels 30 minutes after a glucose load were highest for safflower oil (21.5 mmol/L), modest for rapeseed oil, soybean oil, and lard ( 17.6 mmol/L), mild for perilla, fish, and palm oil ( 13.8 mmol/L), and minimal for high-carbohydrate meals ( 10.4 mmol/L). Only palm oil-fed mice showed fasting hyperinsulinemia (P < .001). By stepwise multiple regression analysis, body weight (or white adipose tissue [WAT] weight) and intake of linoleic acid (or n-3/n-6 ratio) were chosen as independent variables to affect glucose tolerance. By univariate analysis, the linoleic acid intake had a positive correlation with blood glucose level (r = .83, P = .02) but not with obesity (r = .46, P = .30). These data indicate that (1) fasting blood insulin levels vary among fat subtypes, and a higher fasting blood insulin level in palm oil-fed mice may explain their better glycemic control irrespective of their marked obesity; (2) a favorable glucose response induced by fish oil feeding may be mediated by a decrease of body weight; and (3) obesity and a higher intake of linoleic acid are independent risk factors for dysregulation of glucose tolerance.     

Blockade of kinin B(1) receptor reverses plasma fatty acids composition changes and body and tissue fat gain in a rat model of insulin resistance

Aim: Kinin B₁ receptor (B₁R) contributes to insulin resistance through a mechanism involving oxidative stress. This study examined the effect of B₁R blockade on the changes in plasma fatty acids composition, body and tissue fat mass and adipose tissue inflammation that influence insulin resistance. Methods: Sprague–Dawley rats were fed with 10% D‐glucose or tap water (Control) for 13 weeks and during the last week, rats were administered the B₁R antagonist SSR240612 (10 mg/kg/day, gavage) or vehicle. The following parameters were assessed: plasma fatty acids (by gas chromatography), body composition (by EchoMRI), metabolic hormone levels (by radioimmunoassay), expression of B₁R and inflammatory markers in adipose tissue (by Western blot and qRT‐PCR). Results: Glucose feeding significantly increased plasma levels of glucose, insulin, leptin, palmitoleic acid (16:1n‐7), oleic acid (18:1n‐9), Δ6 and Δ9 desaturases while linoleic acid (18:2n‐6), arachidonic acid (20:4n‐6) and Δ5 desaturase were decreased. SSR240612 reduced plasma levels of insulin, glucose, the homeostasis model assessment index of insulin resistance, palmitoleic acid and n‐7 family. Alterations of Δ5, Δ6 and Δ9 desaturases were normalized by SSR240612. The B₁R antagonist also reversed the enhancing effect of glucose feeding on whole body and epididymal fat mass and on the expression of macrophage CD68, interleukin‐1β, tumour necrosis factor‐α and inducible nitric oxide synthase in retroperitoneal adipose tissue. B₁R protein and mRNA were not detected in retroperitoneal adipose tissue. Conclusion: Insulin resistance in glucose‐fed rats is associated with low state inflammation in adipose tissue and plasma fatty acids changes which are reversed by B₁R blockade. These beneficial effects may contribute to insulin sensitivity improvement and the prevention of obesity.     

Diet,fatty acids,and regulation of genes important for heart disease

Diets rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs), such as alpha-linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid, are associated with decreased incidence and severity of coronary heart disease. Similarly, conjugated linoleic acids (CLAs), which are found in meat and dairy products, have beneficial effects against atherosclerosis, diabetes, and obesity. The effects of n3-PUFAs and CLAs are in contrast to fatty acids with virtually identical structures, such as linoleic acid and arachidonic acid (ie, n-6 PUFAs). This article discusses the possibility that cognate receptors exist for fatty acids or their metabolites that are able to regulate gene expression and coordinately affect metabolic or signaling pathways associated with coronary heart disease. Three nuclear receptors are emphasized as fatty acid receptors that respond to dietary and endogenous ligands: peroxisome proliferator activated receptors, retinoid X receptors, and liver X receptors.     

Inhibition of vasopressin-induced formation of diradylglycerols in vascular smooth muscle cells by incorporation of eicosapentaenoic acid in membrane phospholipids.

OBJECTIVE: Eicosapentaenoic acid and linoleic acid exert antihypertensive effects by an unknown mechanism unrelated to prostanoids, a property which is not shared by arachidonic acid. This study investigated the influence of these three acids on the formation of diradylglycerols and phosphatidic acid, key intracellular messengers involved in the mediation of agonist-induced vascular smooth muscle cell contraction. DESIGN: Rat mesenteric artery vascular smooth muscle cells in culture were pre-incubated for 24 h with eicosapentaenoic acid, linoleic acid or arachidonic acid. After thorough washing the cells were then incubated for 20 min in the presence of arginine vasopressin or vehicle, either immediately or following cell labelling with 32P-orthophosphate. METHODS: The fatty acid composition of cell lipids was determined by gas chromatography after transesterification in the presence of boron trifluoride and methanol. Diradylglycerols and 32P-phosphatidic acid were purified from cell lipid extracts by thin-layer chromatography and diradylglycerols were analysed. RESULTS: Incubation of vascular smooth muscle cells with eicosapentaenoic acid, linoleic acid or arachidonic acid resulted in the incorporation of these fatty acids at the sn-2 position of membrane phospholipids, mainly phosphatidylcholine and phosphatidylethanolamine. Eicosapentaenoic acid treatment was associated with a reduction, and linoleic acid treatment with an increase in the relative proportions of arachidonic acid found in cell phospholipids. Arginine vasopressin stimulated the formation of both diradylglycerols and 32P-phosphatidic acid. The arginine vasopressin-induced stimulation of diradylglycerols accumulation was almost completely abolished in eicosapentaenoic acid-treated cells, whereas it was not modified by linoleic acid or by arachidonic acid treatment. The arginine vasopressin-stimulated formation of 32P-phosphatidic acid was significantly inhibited by linoleic acid treatment but was not influenced by eicosapentaenoic acid or arachidonic acid treatment. CONCLUSION: The incorporation of eicosapentaenoic acid or linoleic acid at the sn-2 position of membrane phospholipids leads to an inhibition of arginine vasopressin-induced formation of diradylglycerols or phosphatidic acid, respectively, in rat mesenteric artery vascular smooth muscle cells in culture. These properties may contribute to the antihypertensive effects in these fatty acids in vitro.     

The Role of n-6 Polyunsaturated Fat in Stable Asthmatics

We investigated in a clinical setting whether increased intake of linoleic acid alters respiratory function in 26 mild asthmatics. Subjects completed a 16-week-dietary intervention comprising 8 weeks eating an enriched n-6 polyunsaturated fat diet (9.2% energy from linoleic acid) and consuming either a high monounsaturated or saturated fat diet in a random cross-over resign for 8 weeks. Neither FEV₁ nor PC₂₀ values changed significantly after increased linoleic acid consumption when compared with the other diets. Increased consumption of linoleic acid caused a 20% rise (p ≤ 0.01) in plasma linoleic acid, a 38% decrease (p ≤ 0.01) in plasma eicosapentaenoic acid, but no change in arachidonic acid. There were no changes in symptom scores or bronchodilator use.     

Fatty acid composition of serum cholesterol esters in different degrees of glucose intolerance: a population-based study

The fatty acid composition of serum cholesterol esters was investigated in 325 subjects with normal glucose tolerance, 97 subjects with impaired glucose tolerance (IGT), and 98 subjects with non-insulin-dependent diabetes mellitus (NIDDM) identified by population-based screening. The proportions of palmitic acid (16:0) and palmitoleic acid (16:1) in serum cholesterol esters increased from the normal glucose tolerance group to the IGT and diabetic groups. On the other hand, the proportion of linoleic acid (18:2) was lower in diabetic subjects than in the subjects with IGT or normal glucose tolerance. The proportions of gamma-linolenic (18:3), dihomo-gamma-linoleic (20:3), and arachidonic (20:4) acids were highest in diabetic subjects and lowest in subjects with normal glucose tolerance. Our findings suggest that subjects with NIDDM or IGT have had higher dietary intake of saturated fatty acids. Both serum insulin and blood glucose concentrations probably have an effect on the elongation and desaturation of fatty acids, but the metabolism of linoleic acid to prostaglandin precursors seems to be different in different types of diabetes, NIDDM patients showing no abnormalities. The possibility that the fatty acid composition of plasma and membrane lipids has a role in insulin resistance and blood glucose regulation deserves further investigation.     

Effect of weight and cell size on hormone-induced lipolysis in New Zealand obese mice and American obese hyperglycemic micce

Summary In NZO mice fat cell size is strongly correlated to increasing body weight; FFA and glycerol release from adipose tissue under basal conditions and after stimulation with norepinephrine, ACTH, DB-cyclic AMP and theophylline increase with body weight and fat cell size. Normal weight NZO mice and lean littermates ofobob mice respond similarly to lipolytic agents. — Inobob mice cell size and body weight are correlated until a body weight of about 60 g is reached. Olderobob mice show a decrease in cell size with increasing body weight. There is no correlation between stimulated lipolysis and fat cell size. In these animals an inverse relationship between serum insulin and stimulated lipolysis in adipose tissue was observed. — It is concluded that NZO mice exhibit a type of hypertrophic obesity andobob mice a type of hyperplastic obesity, which may be differentiated by fat cell morphology and the sensitivity of adipose tissue to lipolytic agents.Supported by grants from the Deutsche Forschun-gsgemeinschaft, Bad Godesberg, and Landesamt für Forschung des Landes Nordrhein-Westfalen, Germany.     

Evening primrose oil in rheumatoid arthritis: changes in serum lipids and fatty acids.

The serum concentration of lipids and composition of fatty acids after overnight fasting were studied in 18 patients with rheumatoid arthritis treated for 12 weeks with either 20 ml of evening primrose oil containing 9% of gamma-linolenic acid or olive oil. The serum concentrations of oleic acid, eicosapentaenoic acid, and apolipoprotein B decreased and those of linoleic acid, gamma-linolenic acid, dihomo-gamma-linolenic acid, and arachidonic acid increased during treatment with evening primrose oil. During olive oil treatment the serum concentration of eicosapentaenoic acid decreased and those of high density lipoprotein-cholesterol and apolipoprotein A-I increased slightly. The decrease in serum eicosapentaenoic acid and the increase in arachidonic acid concentrations induced by evening primrose oil may not be favourable effects in patients with rheumatoid arthritis in the light of the roles of these fatty acids as precursors of eicosanoids.     

In vivo and in vitro metabolism in hypothalamic obesity

Summary U-¹⁴C-Glucose was injected into weanling rats two weeks after electrolytic destruction of the ventromedial hypothalamic nuclei. Incorporation of radio-activity into plasma lipids as well as liver, adipose tissue, diaphragm and carcass glycogen, total lipid and saponifiable fatty acids was measured. On a fat free as well as on a chow diet, rats with lesions incorporated more radioativity into all adipose tissue components and into liver fatty acids but not into liver glycogen. On the fat containing diet (chow) radioactivity of plasma lipid was increased and that of liver total lipid unchanged, whereas on a fat-free diet incorporation into plasma lipid was not increased while that into liver lipid was. Diaphragm total lipid and fatty acid radioactivity was increased while that of diaphragm glycogen was not. Carcass lipid, fatty acid and glycogen radioactivity were increased. — Diaphragm was also incubatedin vitro with U-¹⁴C-Glucose or 1-¹⁴C-Palmitate. Glucose incorporation into total lipid and fatty acid was increased whereas oxidation and incorporation into glycogen were not. Palmitate oxidation and incorporation into phospholipid were decreased while incorporation into triglyceride was increased. - Results have been discussed in the light of similar changes previously noted with adipose tissuein vitro.This work was supported by USPHS Grants AM 11746, AM 14418, American Heart Association and Mid-Hudson Heart Association Grants and a V. A. Clinical Investigatorship and Research Grant 01/3193-1/69-01 (J.K.G.).     

ApoE and the role of very low density lipoproteins in adipose tissue inflammation

ObjectiveTo identify the role of triglyceride-rich lipoproteins (TGRLs) and apoE, a major apolipoprotein in TGRLs, in adipose tissue inflammation with high-fat diet (HFD)-induced obesity.MethodsMale apoE^?/? and C57BL/6J wild-type (WT) mice fed HFD for 12 weeks were assessed for metabolic and inflammatory parameters. ApoE^?/? and WT mice were orally gavaged with [³H]palmitic acid to examine the role of apoE in fat delivery to adipose tissue. VLDL from obese apoE^?/? mice were intravenously injected into lean WT or apoE^?/? mice to test potential contribution of TGRLs-derived fat delivery to inflammation in adipose tissue and the role of apoE.ResultsApoE^?/? mice gained less body weight, and had less fat mass and lower triglyceride levels in skeletal muscle than WT. ApoE^?/? mice on HFD had better insulin sensitivity than WT even when comparing body weight-matched mice. Compared to WT mice, apoE^?/? mice on HFD had lower levels of inflammatory cytokines/chemokines and CD11c in adipose tissue, and lower levels of inflammatory markers in skeletal muscle. At 6 h after oral gavage with [³H]palmitic acid, incorporation of [³H]palmitic acid into adipose tissue and skeletal muscle was lower in apoE^?/? mice. After repeated daily injection for 3 days, VLDL from obese apoE^?/? mice induced inflammation in adipose tissue of recipient WT but not apoE^?/? mice.ConclusionIn HFD-induced obesity, apoE plays an important role in inflammation in adipose tissue and skeletal muscle, likely by mediating TGRL-derived fat delivery to these tissues.     

Abnormal fatty acid distribution of the serum phospholipids of patients with non-Hodgkin lymphoma

The data about the fatty acid (FA) status of non-Hodgkin lymphoma (NHL) patients are poor. Therefore, the aim of this study was to investigate the FA profile of serum phospholipids in NHL patients related to the aggressiveness and clinical stage of NHL. We analyzed the FA profile of serum phospholipids in 47 newly diagnosed, untreated NHL patients and in 29 healthy subjects. Significantly higher (p?<?0.001) levels of palmitic (16:0), oleic (18:1 n-9) and arachidonic acids (20:4 n-6), saturated and monounsaturated FA were found in NHL patients, while linoleic acid (18:2 n-6) and the levels of total polyunsaturated FA (PUFA), n-3 PUFA, eicosapentaenoic (20:5 n-3) and docosahexaenoic (DHA, 22:6 n-3) were significantly reduced (p?<?0.01). The level of oleic acid in patients with indolent NHL was significantly lower (p?<?0.05) than in more aggressive types of disease. Contents of palmitoleic acid, docosatetraenoic (22:4 n-6), and PUFA was lower in very aggressive NHL. According to clinical stage (CS), patients with CS I had significantly higher SFA and lower n-6 FA than other three groups, and group with CS IV showed significantly decreased DHA and n-3 PUFA. Our results showed an abnormal FA profile in serum phospholipids in NHL patients.