Prevention of high-fat diet-induced adipose tissue remodeling in obese diabetic mice by n-3 polyunsaturated fatty acids

OBJECTIVE: Obesity is associated with reduced insulin sensitivity and extensive reorganization of adipose tissue. As polyunsaturated fatty acids (PUFA) appear to inhibit diabetes development, we investigated PUFA effects on markers of matrix remodeling in white adipose tissue. METHODS AND PROCEDURE: Male obese diabetic (db/db) mice were treated with either a low-fat standard diet (LF), or high-fat diets rich in saturated and monounsaturated fatty acids (HF/S), n-6 PUFA (HF/6) or the latter including marine n-3 PUFA (HF/3). White adipose tissue was analyzed for gene expression, fatty acid composition and by immunofluorescence. RESULTS: HF/S treatment increased adipose tissue expression of a number of genes involved in matrix degradation including matrix metalloproteinase (MMP)-12, -14 and cathepsin K, L and S compared with LF. MMP-12 gene was expressed in macrophages and adipocytes, and MMP-12 protein colocalized with both cell types. In addition, mean adipocyte area increased by 1.6-fold in HF/S-treated mice. Genes essential for collagen production, such as procollagen I, III, VI, tenascin C and biglycan were upregulated in HF/S-treated animals as well. N-3 PUFA supplementation resulted in enrichment of these fatty acids in adipose tissue. Moreover, n-3 PUFA inhibited the HF/S-induced upregulation of genes involved in matrix degradation and production I restored mean adipocyte area and prevented MMP-12 expression in macrophages and adipocytes. CONCLUSION: N-3 PUFA prevent high-fat diet-induced matrix remodeling and adipocyte enlargement in adipose tissue of obese diabetic mice. Such changes could contribute to diabetes prevention by n-3 PUFA in obese patients.     

Steatosis and Collagen Content in Experimental Liver Cirrhosis Are Affected by Dietary Monounsaturated and Polyunsaturated Fatty Acids

Background and Methods: We used thioacetamide administered orally to induce cirrhosis in rats, and after these had recovered for 1 and 2 weeks we examined the effects of dietary supplementation with monounsaturated and n-3 polyunsaturated fatty acids, or with a combination of n-3 and n-6 polyunsaturated fatty acids, on the extent of steatosis and collagen content in the liver. Results: Nodular cirrhosis, increased collagen content, and lipid accumulation were established after 4 months of treatment with thioacetamide. When the animals were fed a diet rich in oleic acid for 2 weeks, the steatosis and fibrosis decreased. Supplementation with n-3 polyunsaturated fatty acids favored reductions in collagen content but did not reduce the fat accumulation. With a diet supplemented with a mixture of n-3 and n-6 fatty acids we found no reduction in either lipid accumulation or collagen content. Conclusions: Fibrosis and steatosis may be influenced by dietary fat, and monounsaturated fat appears to influence favorably the histologic recovery of the damaged liver.     

Effects of long-chain monounsaturated and n-3 fatty acids on fatty acid oxidation and lipid composition in rats

Long-chain n-3 fatty acids and fat fish are reported, among multiple physiological properties, to enhance peroxisomal beta-oxidation and effect triacylglycerol status. Long-chain n-3 and monounsaturated fatty acids are the main portion of fatty acids in fat fish. The individual effect of long-chain monounsaturated fatty acids on beta-oxidation and fatty acid composition was tested and compared to the effect of n-3 polyunsaturated and saturated fatty acids in a 3-week feeding experiment of rats. To explore the contribution from long-chain monounsaturated fatty acids in these aspects, the effect of long-chain n-3 and monounsaturated fatty acids on mitochondrial and peroxisomal beta-oxidation was compared, as well as fatty acid composition of adipose tissue, liver and serum. Fatty acid oxidase, palmitoyltransferase I and II activities, the amount of serum lipids, and the fatty acid composition of lipid fractions from the organs were analysed. The peroxisomal beta-oxidation was enhanced by the n-3 fatty acids, whereas a small, significant increase with the monounsaturated fatty acids was observed. There was a stimulation of the mitochondrial oxidation with the n-3 fatty acids, but monounsaturated fatty acids gave a small, nonsignificant decrease. With n-3 fatty acids there was a considerable decrease in the levels of serum triacylglycerol, phospholipids, free fatty acids and total cholesterol, while there were only minor effects of monounsaturated fatty acids. As judged from the fatty acid composition data, there was a mobilization on n-3 fatty acids from the adipose tissue to liver and plasma with the n-3 diet. This observation was also seen with the monounsaturated fatty acid-enriched diet. In conclusion, monounsaturated fatty acids seemed to stimulate peroxisomal beta-oxidation and to increase plasma triacylglycerol, whereas the mitochondrial oxidation was slightly decreased.     

Adipose tissue inflammation induced by high-fat diet in obese diabetic mice is prevented by n−3 polyunsaturated fatty acids

Aims/hypothesis Inflammatory alterations in white adipose tissue appear to underlie complications of obesity including diabetes mellitus. Polyunsaturated fatty acids (PUFA), particularly those of the n−3 series, modulate immune responses and may ameliorate insulin sensitivity. In this study, we investigated how PUFA affect white adipose tissue inflammation and gene expression in obese diabetic animals.Materials and methods We treated db/db mice as well as lean non-diabetic mice (db/+) with either low-fat standard diet (LF) or high-fat diets rich in (1) saturated/monounsaturated fatty acids (HF/S), (2) n−6 PUFA (HF/6) and (3) the latter including purified marine n−3 PUFA (HF/3).Results Many genes involved in inflammatory alterations were upregulated in db/db mice on HF/S compared with LF in parallel with phosphorylation of c-Jun N-terminal kinase (JNK). In parallel, adipose tissue infiltration with macrophages was markedly enhanced by HF/S. When compared with HF/S, HF/6 showed only marginal effects on adipose tissue inflammation. However, inclusion of n−3 PUFA in the diet (HF/3) completely prevented macrophage infiltration induced by high-fat diet and changes in inflammatory gene expression, also tending to reduce JNK phosphorylation (p<0.1) in diabetic mice despite unreduced body weight. Moreover, high-fat diets (HF/S, HF/6) downregulated expression and reduced serum concentrations of adiponectin, but this was not the case with n−3 PUFA.Conclusions/interpretation n−3 PUFA prevent adipose tissue inflammation induced by high-fat diet in obese diabetic mice, thereby dissecting obesity from adipose tissue inflammation. These data suggest that beneficial effects of n−3 PUFA on diabetes development could be mediated by their effect on adipose tissue inflammation. Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.     

Modifications of alpha-tocopherol and fatty acid concentrations in blood and adipose tissue of obese patients during a weight loss programme

BACKGROUND AND AIM: The aim of the study was to describe qualitative and/or quantitative modifications of lipoproteins, including their fatty acid composition, in obese patients during a hypocaloric diet, and determine whether the variations observed paralleled modifications of alpha-tocopherol concentration in adipose tissue and blood. METHODS AND RESULTS: 15 healthy, obese volunteers (5 males, 10 females; age: 32-69 yr; BMI: 28.4-60.5 kg/m2) were given a 3-week hypocaloric diet (3.9 MJ (941 kcal)). Adipose tissue and blood samples were taken at the beginning and at the end of this period. At baseline and after 3 weeks measurements were made for alpha-tocopherol and fatty acids in total serum, lipoproteins and adipose tissue; thiobarbituric acid-reactive substances (TBARS) in serum. A significant drop in cholesterol-rich particles (LDL and HDL) was observed, in parallel to a significant enrichment of n-6 polyunsaturated fatty acids (PUFA) at the expense of both saturated and monounsaturated fatty acids in serum. A drop in alpha-tocopherol concentration (expressed as mumol alpha-tocopherol/g lipid) in serum and lipoprotein fractions paralleled the decrease in cholesterol-rich lipoproteins. CONCLUSIONS: Our results suggest that a hypocaloric diet not only decreases cholesterol-rich particle levels in serum, but also leads to a significant modification of fatty acid composition which may reflect improvement of insulin sensitivity. We did not observe any modification in adipose tissue after diet with regard to both alpha-tocopherol and fatty acid concentrations. Despite a drop in alpha-tocopherol concentration and an increase in n-6 PUFA content in serum, we did not find any enhancement of serum lipid peroxidation level evaluated by the thiobarbituric acid-reactive substance (TBARS) assay. If we assume that dietary intakes of alpha-tocopherol were not modified during this diet, it can be supposed that adipose tissue released alpha-tocopherol without any specific regulation, in parallel to the release of fatty acids.     

Comparison of the Effects on the Diurnal Blood Pressure,Glucose, and Lipid Levels of a Diet Rich in Monounsaturated Fatty Acids With a Diet Rich in Polyunsaturated Fatty Acids in Type 2 Diabetic Subjects

The influence on blood pressure, glucose metabolism, and lipid levels of an exchange of polyunsaturated fatty acids with monounsaturated fatty acids in the diet was compared in 16 Type 2 diabetic outpatients. In a cross-over study design the patients were randomly assigned to 3 weeks treatments with a diet containing 30% energy as monounsaturated fatty acids, or an isoenergetic diet with 30% energy as polyunsaturated fatty acids. The contents of total fat, satuarated fatty acids, cholesterol, and fibre were similar in the two diets. On the last days of the two diet periods, 24-h ambulatory blood pressure was measured and the responses of glucose, hormones, and lipids to a carbohydrate rich test meal were measured. As compared with the polyunsaturated fatty acids diet, the monounsaturated fatty acids diet reduced 24-h systolic (129 ± 11 vs 124 ± 8 mmHg (mean ± SD), p = 0.02) and diastolic blood pressure (76 ± 11 vs 73 ± 8 mmHg, p = 0.02). The two diets had similar, beneficial effects on glycaemic control, and cholesterol and lipoprotein concentrations. A diet rich in monounsaturated fatty acids has beneficial effects on the blood pressure, while similar effects on glucose and lipid levels are observed in normotensive Type 2 diabetic subjects.     

Site dependency of fatty acid composition in adipose triacylglycerol in rats and its absence as a result of high-fat feeding

It is currently believed that metabolic syndrome, in general, and type 2 diabetes mellitus, in particular, depend more on visceral than on subcutaneous adipose tissue. However, the relationship between insulin resistance and fatty acid composition in visceral and subcutaneous adipose tissues remains to be clarified. In the present study, we extracted the triacylglycerol from visceral (epididymis and mesentery) and subcutaneous adipose tissues in normal and insulin-resistant, high-fat-fed (HFF) rats and determined the composition of each fatty acid. The concentrations of palmitoleic, docosapentaenoic, docosahexaenoic, dihomo-γ-linolenic, arachidonic, and docosatetraenoic acids were higher in epididymal adipose tissue than in mesenteric and subcutaneous adipose tissues; but no significant differences were detected between mesenteric and subcutaneous tissues in the normal group or among all the sites in the HFF rats. In the HFF group, stearic and oleic acid concentrations were higher, whereas n-3 and n-6 polyunsaturated ones were lower, than those in the normal group. Palmitoleic acid and some n-3 and n-6 polyunsaturated fatty acid compositions in adipose tissue triacylglycerol depend on anatomical location, which may affect the properties and/or function of adipose tissues. These results at least in part suggest that the properties of adipose tissue are difficult to distinguish based only on their "visceral" or "subcutaneous" sites. In addition, the absence of site dependence and/or difference in balance among saturated, monounsaturated, and polyunsaturated fatty acids may play an important role in the development of insulin resistance in the HFF rats.     

The -514 C/T polymorphism in the hepatic lipase gene promoter is associated with insulin sensitivity in a healthy young population

Impaired insulin action has been associated with diabetes, dyslipidemia and atherosclerotic vascular disease. The expression of insulin resistance results from the interaction of environmental and genetic factors. Human hepatic lipase (HL) is a lipolytic enzyme that plays a role in the metabolism of several lipoproteins, while insulin up-regulates the activity of HL via insulin-responsive elements in the HL promoter. We have examined the influence of -514 C/T polymorphism in the hepatic lipase gene promoter on insulin sensitivity in 59 healthy young subjects (30 males and 29 females). The volunteers were subjected to three dietary periods, each lasting four weeks. During the first period all subjects consumed a saturated fat (SFA)-enriched diet with 38% as fat (20% SFA, 12% monounsaturated fatty acids (MUFA) and 6% polyunsaturated fatty acids (PUFA)). In the second and third dietary periods, a randomized crossover design was used, consisting of a low fat, high carbohydrate diet (CHO diet) (< 10% SFA, 12% MUFA and 6% PUFA) and a high-MUFA, or Mediterranean diet, with < 10% SFA, 22% MUFA and 6% PUFA. We determined the in vivo insulin resistance using the insulin suppression test with somatostatin. Steady-state plasma glucose (SSPG) concentrations (a measure of insulin sensitivity) were significantly higher in men carriers of the -514T allele after the consumption of the SFA diet than after the CHO diet and the Mediterranean diet. This effect was not observed in women. Moreover, there were no significant differences in insulin sensitivity after the three diets in men and women with the CC genotype. In summary, our results show an improvement in insulin sensitivity in men with the -514T allele of the HL promoter polymorphism, when MUFA and carbohydrates are consumed instead of SFA fat.     

The influence of dietary fat on insulin resistance

Dietary fat has been implicated in the development of insulin resistance in both animals and humans. Most, although not all, studies suggest that higher levels of total fat in the diet result in greater whole-body insulin resistance. Although, in practice, obesity may complicate the relationship between fat intake and insulin resistance, clinical trials demonstrate that high levels of dietary fat can impair insulin sensitivity independent of body weight changes. In addition, it appears that different types of fat have different effects on insulin action. Saturated and certain monounsaturated fats have been implicated in causing insulin resistance, whereas polyunsaturated and omega-3 fatty acids largely do not appear to have adverse effects on insulin action. Given the importance of insulin resistance in the development of diabetes and heart disease, establishing appropriate levels of fat in the diet is an important clinical goal.     

Influence of dietary fat on the lipid composition of perirenal adipose tissue in rats

The influence of dietary fat on the composition of perirenal adipose tissue was studied in Wistar rats fed three experimental semisynthetic, isocaloric diets containing different qualities of fat (olive oil, butter and medium chain triglycerides + corn oil). Under these experimental conditions, the saturation index reflects the percentage of fatty acids supplied by each diet; this index was highest in animals fed the diet containing butter and lowest in the group in which olive oil was the dietary fat source. The amount of linoleic acid (the major component of the diunsaturation index) supplied by the diet is directly paralleled by levels of this fatty acid in perirenal adipose tissue, whereas the monounsaturation index in adipose tissues, considered an indicator of the dietary supply of monounsaturated fatty acids in the rat, failed to show a clearly proportional relationship between intake and perirenal adipose tissue levels.     

Specific alterations in different adipose tissues of pig adipocyte plasma membrane structure by dietary lipids

The effect of dietary n-6 polyunsaturated fatty acid content on pig adipocyte plasma membrane was studied with two types of adipose tissues: subcutaneous backfat layer and perirenal fat. When pigs were fed a diet containing 15 percent sunflower oil, the n-6 polyunsaturated fatty acid content in the membranes increased in both tissues parallel to a decrease in the n-9 monounsaturated fatty acid content. An increase in membrane fluidity measured by fluorescence polarization was observed particularly in subcutaneous tissue, in spite of a higher level of some membrane rigid components: the sphingomyelin/phosphatidylcholine ratio was increased in the subcutaneous tissue, whereas the cholesterol/phospholipid ratio was increased in the perirenal one. The latter results gave evidence for a depot-dependent modification in the membrane structure by dietary lipids.     

Trans-10,cis-12-CLA-caused lipodystrophy is associated with profound changes of fatty acid profiles of liver, white adipose tissue and erythrocytes in mice: possible link to tissue-specific alterations of fatty acid desaturation

Dietary supplementation with conjugated linoleic acid (CLA) has been shown to reduce body fat mass. To investigate the effects of individual CLA isomers on the fatty acid profiles of lipogenic (liver and white adipose) and lipid sensitive (erythrocyte) tissues, BALB/c mice were fed with 1 of 2 diets supplemented with either a c9,t11-CLA-enriched and t10,c12-CLA-free or a CLA-mixture containing both isomers in equal amounts (1% w/w of the diet) for 5 weeks. A control group was fed with a diet enriched in sunflower oil to energy balance the CLA. Compared to the t10,c12-CLA-free and the control diets, we observed a significant reduction of adipose tissue accompanied by fatty livers in the CLA-mix-fed group. These alterations in body fat distribution entailed a conspicuous shift of the fatty acid profiles of adipose tissue and livers. Liver enlargement was mainly caused by accumulation of C18 monoenes that accounted for 67 ± 1% of total fatty acid methyl esters. The significant reduction of the 18:0/18:1 desaturation index in the liver upon CLA-mix diet indicated high stearoyl-CoA desaturase activity. In contrast, reduction in white adipose tissue was largely driven by percental reduction of monounsaturated fatty acids (p ≤ 0.001). 16:0/ 16:1 and 18:0/18:1 desaturation indices for white adipose tissue significantly increased, suggesting an inhibition of stearoyl-CoA desaturase upon CLA-mix diet. The fatty acid profile of the erythrocytes widely reflected that of livers, depending on the supplemented diet. These profound changes in fatty acid composition of lipogenic organs due to t10,c12-CLA intake may be the consequence of functional alterations of lipid metabolism.     

Urinary albumin excretion rate and 24-h ambulatory blood pressure in NIDDM with microalbuminuria: effects of a monounsaturated-enriched diet

Summary Previous studies have shown that unsaturated fat-enriched diets may have a beneficial effect on blood pressure in non-insulin-dependent diabetic (NIDDM) patients, whereas little is known about the effects on albuminuria. In a 3-week cross-over design we compared the effects of a currently recommended high-carbohydrate diet (50% carbohydrate, 30% fat [10% monounsaturated fat]) vs a diet rich in monounsaturated fat (30% carbohydrate, 50% fat [30% monounsaturated fat]) on urinary albumin excretion rate, 24-h ambulatory blood pressure and metabolic control in ten NIDDM patients with persistent microalbuminuria. The 24-h ambulatory blood pressure was similar before and after both the high-carbohydrate diet (mean±SD: 145/78±25/10 vs 143/79±19/10 mmHg (NS) and the monounsaturated fat diet: 140/78±16/8 vs 143/79±15/8 mmHg (NS). No changes were observed in day or night-time blood pressures. Urinary albumin excretion rate was unaffected after 3 weeks' treatment by the diets: from (geometric mean ×/÷ tolerance factor) 32.4×/÷2.1 to 36.0×/÷1.9 g/min (NS) vs from 34.2×/÷1.9 to 32.1×/÷2.1 g/min (NS). Fasting plasma glucose, serum fructosamine and HbA_1c as well as lipid and lipoprotein concentrations were stable during both diets. Compared to the high-carbohydrate diet a reduction in the LDL/HDL cholesterol ratio was observed during the monounsaturated fat diet (p<0.03). In conclusion, compared to a high-carbohydrate diet, 3 weeks' treatment with a monounsaturated fat diet did not affect the levels of 24-h ambulatory blood pressure or albuminuria in microalbuminuric NIDDM patients. Moreover, glycaemic control and lipoprotein levels were unchanged, although a potential beneficial effect on the LDL/HDL-cholesterol ratio was noted. Monounsaturated fat represents an alternative in the diets of NIDDM patients especially when caloric intake is not a concern.Abbreviations UAE Urinary albumin excretion rate - NIDDM non-insulin-dependent diabetes mellitus - MUFA monounsaturated fatty acids - PUFA polyunsaturated fatty acids - ANOVA analysis of variance - CHO carbohydrate - CI confidence interval     

Fiber type- and fatty acid composition-dependent effects of high-fat diets on rat muscle triacylglyceride and fatty acid transporter protein-1 content

Intramuscular triacylglyceride (TAG) is considered an independent marker of insulin resistance in humans. Here, we examined the effect of high-fat diets, based on distinct fatty acid compositions (saturated, monounsaturated or n-6 polyunsaturated), on TAG levels and fatty acid transporter protein (FATP-1) expression in 2 rat muscles that differ in their fiber type, soleus, and gastrocnemius; the relationship to whole body glucose intolerance was also studied. Compared with carbohydrate-fed rats, the groups subjected to any one of the high-fat diets consistently exhibited enhanced body weight gain and adiposity, elevated plasma free fatty acids and TAG in the fed condition, hyperinsulinemia, and glucose intolerance. TAG content was consistently higher in soleus than in gastrocnemius, but was only significantly elevated by the n-6 polyunsaturated-based diet. FATP-1 levels in soleus were double those in gastrocnemius muscle in carbohydrate-fed animals. High-fat diets caused an elevation in FATP-1 protein content in soleus, but a reduction in gastrocnemius. In conclusion, the hyperinsulinemic hyperlipidemic condition upregulates FATP-1 expression in soleus and downregulates that of gastrocnemius. Hypercaloric saturated, monounsaturated, or n-6 polyunsaturated lipid diets cause equivalent whole body insulin resistance in rats, but only an n-6 polyunsaturated acid-based diet triggers intramuscular TAG accumulation.     

A high-trans fatty acid diet and insulin sensitivity in young healthy women.

Epidemiological and experimental studies suggest that a diet rich in saturated fat affects insulin sensitivity. Monoenes and dienes that have an usaturated bond with the trans configuration (trans fatty acids) resemble saturated fatty acids with respect to structure, but no published data are available on the effect of trans fatty acids on insulin sensitivity. Therefore, the effects of diets high in trans fatty acids (TFA diet) and oleic acid (monounsaturated fat [MUFA] diet) on glucose and lipid metabolism were studied in 14 healthy women. Subjects consumed both experimental diets for 4 weeks according to a randomized crossover study design. Both experimental diet periods were preceded by consumption of a standardized baseline diet for 2 weeks. The diets provided 36.6% to 37.9% of energy (E%) as fat. In the TFA diet, there was 5.1 E% trans fatty acids, and in the MUFA diet, 5.2 E% oleic acid, substituted for saturated fatty acids in the baseline diet. A frequently sampled intravenous glucose tolerance test (FSIGT) was performed at the end of the experimental diet periods. Glucose effectiveness (S(G)) and the insulin sensitivity index (S(I)) did not differ after the two experimental diet periods. There was also no difference in the acute insulin response between the diets. The total cholesterol to high-density lipoprotein (HDL) cholesterol ratio and serum total triglyceride, HDL, and low-density lipoprotein (LDL) triglyceride and apolipoprotein B (apoB) concentrations were higher (P < .05) after the TFA diet. In conclusion, in young healthy women, the TFA diet resulted in a higher total/HDL cholesterol ratio and an elevation in triglyceride and apo B concentrations but had no effect on glucose and insulin metabolism compared with the MUFA diet.     

Balanced high fat diet reduces cardiovascular risk in obese women although changes in adipose tissue,lipoproteins, and insulin resistance differ by race

BackgroundWe previously reported that consuming a balanced high fat diet (BHFD) wherein total saturated fat was reduced and total unsaturated fat increased by proportionately balancing the type of fat (1/3 saturated, 1/3 monounsaturated, 1/3 polyunsaturated) led to significant improvements in inflammatory burden, blood pressure, and vascular function in obese premenopausal European American (EA) and African American (AA) women.ObjectiveHere we compared changes in adipose tissue, lipoproteins, insulin resistance, and cardiovascular risk between EA and AA women.MethodsDietary intakes, plasma fatty acids, lipids, apolipoproteins, lipoproteins, HOMA-IR and ASCVD risk was measured in 144 women who consumed BHFD for 16 weeks. Generalized linear modeling was performed while controlling for change in body weight.ResultsEA women had greater reductions in visceral adipose tissue. Only EA women had significant reductions in fasting insulin levels (↓24.8%) and HOMA-IR (↓29%) scores. In EA women, the most significant improvements occurred in VLDL particle size (↑), apolipoprotein B levels (↑), serum TG (↓), number of plasma LDL particles (↓), and serum LDL-cholesterol (↓). In AA women, significant improvements occurred in HDL particle size (↑), number of large HDL particles (↑), and apolipoprotein AI levels (↑). Consequently, both groups had improved ASCVD risk scores (↓5.5%).ConclusionsConsuming the balanced high fat diet led to significant reduction in cardiovascular risk factors in both groups. However, the pattern of response to BHFD differed with EA women responding more in components of the apolipoprotein B pathway versus AA women responding more in components of the apolipoprotein AI pathway.     

Interaction between specific fatty acids,GLP-1 and insulin secretion in humans

AIMS/HYPOTHESIS: Fatty acids affect insulin secretion in vivo, but little is known about the effects of specific fatty acids. Our aim was to investigate differential effects of acutely increased plasma monounsaturated, polyunsaturated and saturated fatty acids on glucose-stimulated insulin secretion in healthy humans. METHODS: A new experimental protocol was used to increase plasma monounsaturated (MUFA test), polyunsaturated (PUFA test) or saturated (SFA test) non-esterified fatty acids for 2 h by repeated oral fat feeding and continuous intravenous heparin infusion. This was followed by a hyperglycaemic clamp (10 mmol/l) to test insulin secretion in response to a prior plasma NEFA increase. RESULTS: Total plasma NEFA concentrations were increased during the fat tests compared to the control visit (1.7-fold increase for MUFA and SFA tests and 1.4-fold increase for PUFA test; p<0.001). Exaggerated responses in plasma insulin, C-peptide and proinsulin concentrations were seen during the hyperglycaemic clamp after increasing plasma NEFA concentrations compared with the control (p<0.01). The effects were greatest for the MUFA test followed by the PUFA test and SFA test (p<0.01). Plasma GLP-1 concentrations increased during fat feeding, with a higher response during the MUFA test compared to PUFA and SFA tests (p<0.01). CONCLUSION/INTERPRETATION: Increasing plasma NEFA concentrations by oral fat feeding with heparin infusion augments glucose-stimulated insulin secretion with the greatest effect for monounsaturated fatty acids and the lowest effect for saturated fatty acids. Monounsaturated fatty acids also increase GLP-1 more than saturated fatty acids. Therefore, the exaggerated insulin concentrations could be due to both NEFA and GLP-1.     

Substituting dietary saturated fat with polyunsaturated fat changes abdominal fat distribution and improves insulin sensitivity

Aims/hypothesis: British dietary recommendations are to decrease total fat intake to less than 30 % of daily energy intake and saturated fat to less than 10 %. In practice, it is difficult for people to make these changes. It may be easier to encourage people to switch from a diet rich in saturated fatty acids to one rich in polyunsaturated fatty acids. Methods: A total of 17 subjects – six people with Type II (non-insulin-dependent) diabetes mellitus, six non-obese and five obese people without diabetes – were randomised to spend two 5-week periods on a diet rich in saturated or in polyunsaturated fatty acids, in a crossover design. At the start of the study and after each dietary period, we assessed abdominal fat distribution using magnetic resonance imaging, insulin sensitivity using hyperinsulinaemic-euglycaemic clamps and fasting lipid parameters. Results: Dietary compliance, assessed by weekly 3-day dietary records and measurement of biochemical markers, was good. Energy and fat intake appeared to be reduced on the diet rich in polyunsaturated fatty acids although body weights did not change. Insulin sensitivity and plasma low density lipoprotein cholesterol concentrations improved with the diet rich in polyunsaturated fatty acids compared with the diet rich in saturated fatty acids. There was also a decrease in abdominal subcutaneous fat area. Conclusion/interpretation: If this result is confirmed in longer-term studies, this dietary manipulation would be more readily achieved by the general population than the current recommendations and could result in considerable improvement in insulin sensitivity, reducing the risk of developing Type II diabetes. [Diabetologia (2002) 45: 369–377] Received: 3 August 2001 and in revised form: 26 November 2001     

小檗碱对实验大鼠糖脂代谢的影响

目的探讨小檗碱对实验大鼠胰岛素敏感性和血糖血脂的影响。方法实验大鼠分7组：普食对照组和小檗碱治疗组，高脂对照组和小檗碱治疗组，高脂饮食与极小剂量链脲佐菌素(STZ)诱导的糖尿病对照组，糖尿病小檗碱治疗组和二甲双胍治疗组。疗程为5周。以糖耐量试验评估胰岛功能，以胰岛素耐量试验中的降糖率检测胰岛素敏感性。结果(1)小檗碱使糖尿病鼠的降糖率升高48％，疗效较二甲双胍为好；小檗碱使高脂鼠的胰岛素敏感因子升高78％，延缓了普食鼠降糖率的下降；(2)小檗碱显著降低了高脂大鼠的空腹血糖和负荷血糖；(3)小檗碱使普食鼠、高脂鼠和糖尿病鼠的血清游离脂肪酸分别下调14％、24％和20％，使高脂鼠的血清甘油三酯降低57％。结论小檗碱有显著的胰岛素增敏和降低血清游离脂肪酸的作用，并能降低高脂大鼠的血糖。     

Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU study

Aims/hypothesis. The amount and quality of fat in the diet could be of importance for development of insulin resistance and related metabolic disorders. Our aim was to determine whether a change in dietary fat quality alone could alter insulin action in humans. Methods. The KANWU study included 162 healthy subjects chosen at random to receive a controlled, isoenergetic diet for 3 months containing either a high proportion of saturated (SAFA diet) or monounsaturated (MUFA diet) fatty acids. Within each group there was a second assignment at random to supplements with fish oil (3.6 g n-3 fatty acids/d) or placebo. Results. Insulin sensitivity was significantly impaired on the saturated fatty acid diet (-10 %, p = 0.03) but did not change on the monounsaturated fatty acid diet ( + 2 %, NS) (p = 0.05 for difference between diets). Insulin secretion was not affected. The addition of n-3 fatty acids influenced neither insulin sensitivity nor insulin secretion. The favourable effects of substituting a monounsaturated fatty acid diet for a saturated fatty acid diet on insulin sensitivity were only seen at a total fat intake below median (37E %). Here, insulin sensitivity was 12.5 % lower and 8.8 % higher on the saturated fatty acid diet and monounsaturated fatty acid diet respectively (p = 0.03). Low density lipoprotein cholesterol (LDL) increased on the saturated fatty acid diet ( + 4.1 %, p < 0.01) but decreased on the monounsaturated fatty acid diet (MUFA) (–5.2, p < 0.001), whereas lipoprotein (a) [Lp(a)] increased on a monounsaturated fatty acid diet by 12 % (p < 0.001). Conclusions/interpretation. A change of the proportions of dietary fatty acids, decreasing saturated fatty acid and increasing monounsaturated fatty acid, improves insulin sensitivity but has no effect on insulin secretion. A beneficial impact of the fat quality on insulin sensitivity is not seen in individuals with a high fat intake ( > 37E %). [Diabetologia (2001) 44: 312–319] Received: 21 August 2000 and in revised form: 8 November 2000