Nobuyo Tsunoda

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% alpha-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 > or = lard > or = rapeseed > or = safflower > or = perilla > fish oil. Glucose levels 30 minutes after a glucose load were highest for safflower oil (approximately 21.5 mmol/L), modest for rapeseed oil, soybean oil, and lard (approximately 17.6 mmol/L), mild for perilla, fish, and palm oil (approximately 13.8 mmol/L), and minimal for high-carbohydrate meals (approximately 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.

TRPV1 Agonist Monoacylglycerol Increases UCP1 Content in Brown Adipose Tissue and Suppresses Accumulation of Visceral Fat in Mice Fed a High-Fat and High-Sucrose Diet

The administration of such a transient receptor potential vanilloid 1 (TRPV1) agonist as capsaicin, which is a pungent ingredient of red pepper, promotes energy metabolism and suppresses visceral fat accumulation. We have recently identified monoacylglycerols (MGs) having an unsaturated long-chain fatty acid as the novel TRPV1 agonist in foods. We investigated in this present study the effects of dietary MGs on uncoupling protein 1 (UCP1) expression in interscapular brown adipose tissue (IBAT) and on fat accumulation in mice fed with a high-fat, high-sucrose diet. The MG30 diet that substituted 30% of all lipids for MGs (a mixture of 1-oleoylglycerol, 1-linoleoylglycerol and 1-linolenoylglycerol) significantly increased the UCP1 content of IBAT and decreased the weight of epididymal white adipose tissue, and the serum glucose, total cholesterol and free fatty acid levels. The diet containing only 1-oleoylglycerol as MG also increased UCP1 expression in IBAT. MGs that activated TRPV1 also therefore induced the expression of UCP 1 and prevented visceral fat accumulation as well as capsaicin.

Peroxisome proliferator-activated receptors (PPARs)-independent functions of fish oil on glucose and lipid metabolism in diet-induced obese mice

BackgroundFish oil is known to improve lifestyle-related diseases. These effects occur partly via activation of PPARs by the n-3 polyunsaturated fatty acids included abundantly in fish oil. We investigated fish oil functions on glucose and lipid metabolism that are both dependent on and independent of PPARs pathway.MethodsMice were fed a diet containing 30 en% beef tallow (B diet) for twelve weeks to induce obesity. The mice were then divided into two groups which were fed either a B diet or a diet containing 30 en% fish oil (F diet). Each group was further divided into two groups which were administered PPARα and γ antagonists or vehicle once a day for three weeks.ResultsThe F diet groups showed lower triglyceride levels in plasma and liver than the B diet groups, but PPARs antagonists did not affect the triglyceride levels in either diet groups. The F diet groups also showed improvement of glucose tolerance compared with the B diet groups. However, PPARs antagonists made glucose tolerance worse in the F diet group but improved it in the B diet group. Therefore, by the administration of antagonists, glucose tolerance was inversely regulated between the B and F diets, and hypolipidemic action in the plasma and liver of the F diet group was not affected.ConclusionThese results suggest that fish oil decreases lipid levels in plasma and liver via PPARs pathway-independent mechanism, and that glucose tolerance is inversely regulated by PPARs antagonists under diets containing different oils.

Dose-dependent effects, safety and tolerability of fenugreek in diet-induced metabolic disorders in rats

BackgroundWe previously reported that fenugreek (Trigonella foenum-graecum L.) improved diet-induced metabolic disorders in rats. The purpose of the present study was to examine the dose-dependent effects, safety and tolerability of fenugreek.MethodsThe diets used in this study were the high-fat high-sucrose diet (HFS; lard 50%kcal, sucrose 25%kcal) as a control (Ctrl group) or the HFS containing 0.25% (VL group), 1.25% (L group), 2.50% (M group), 5.00% (H group) or 12.30% (VH group) fenugreek based on the modified version of the AIN-93G purified diet.ResultsFenugreek dose-dependently reduced the hepatic triglyceride and total cholesterol levels. Fenugreek also dose-dependently increased the excretion of cholesterol and total bile acids into the feces. However, the glucose tolerance showed no significant change by fenugreek administration. The VL and L groups did not significantly change triglyceride or total cholesterol levels in the liver. The VL group showed no increase in excretion of triglyceride, total cholesterol or bile acids in the feces. The VH group showed appetite reduction and diarrhea, while no adverse effect or symptoms were observed in the M group.ConclusionThese results suggest that fenugreek inhibited lipid accumulation in the liver by increasing the lipid excretion in the feces. The effective, safe and tolerable dose of fenugreek was found to be around 2.50% (w/w).

Regulation of Lipid Metabolism by Palmitoleate and Eicosapentaenoic Acid (EPA) in Mice Fed a High-Fat Diet

We investigated whether oral administration of palmitoleate ameliorates disorders of lipid metabolism to clarify the effects of one of the components of fish oil. Lipid levels in the liver and plasma were significantly decreased by palmitoleate and by EPA administration. These results suggest that palmitoleate, in addition to EPA, plays a role in the regulation of lipid metabolism by fish oil.

Effects of a comprehensive intervention program, including hot bathing, on overweight adults: a randomized controlled trial.

The objective of this study was to evaluate the effects of a comprehensive overweight intervention program, which utilizes hot bathing, on overweight, community‐dwelling middle‐aged and older adults in a randomized controlled trial.

Improvement in the High-Fat Diet-Induced Dyslipidemia and Adiponectin Levels by Fish Oil Feeding Combined with Food Restriction in Obese KKAy Mice

The effect on weight reduction of fish oil combined with food restriction in comparison with that of beef tallow was investigated in high-fat diet-induced obese KKAy mice. Although the reduction of body and white adipose tissue weight was similar in the two groups, fish oil increased adiponectin levels in the plasma, improved dyslipidemia accompanied by suppression of lipid synthesis in the liver when compared with beef tallow.

Fenugreek Improves Diet-induced Metabolic Disorders in Rats

Trigonella foenum-graecum L. (fenugreek) has been described earlier and its use in ancient medicinal practice is well known. The hypoglycemic effects of fenugreek have been studied in many animal models and diabetic patients. The purpose of this study was to examine the preventive efficiency of dietary fenugreek on diet-induced metabolic diseases in rats. The diets used in this study were a standard diet, a high-fat high-sucrose (HFS) diet, and a HFS diet containing 0.5 g/kg b. w./day fenugreek based on the modified version of the AIN-93G purified diet, for 12 weeks, respectively. The rats fed the HFS diet containing fenugreek showed significantly lower fasting insulin levels and HOMA-IR than the rats fed the HFS diet. Therefore, fenugreek improved insulin sensitivity in rats. The triglyceride and total cholesterol levels in the plasma were significantly lower in the fenugreek-administered group. Moreover, distinct reductions of triglyceride, total cholesterol, free fatty acid, and phospholipid levels in the liver were found in the rats fed the HFS diet containing fenugreek. These results suggest that fenugreek enhanced insulin sensitivity at least partly by improving lipid metabolism disorders in the plasma and the liver in the rats induced by the HFS diet.

Arginine-induced insulin secretion in endoplasmic reticulum.

Arginine, a semi-essential amino acid, is known as one of the most strongest insulin secretagogues in a glucose-dependent manner, but major mechanism is unknown. Arginine induced insulin secretion in mice as well as β cell line, NIT-1, in which more than 90% of intracellular insulin is prionsulin without arginine cultivation. Arginine administration reduced prionsulin amount in 30 s, then insulin is secreted from NIT1 cells. These data indicated that the target factor(s) for arginine-induced insulin secretion located in endoplasmic reticulum (ER). We established the screening system for identifying the arginine mimetics. Brazilian propolis, not Chinese propolis, induced insulin secretion. To identify target factor(s) of arginine induced insulin secretion, our previous study was that nanobeads technology facilitated us to purify chemical-target factors. This time we chose the other way, proinsulin associating factor purification and arginine-immobilized agarose. Three proinsulin associating factors and 5 arginine interacting factors were identified. Among theses factors, Calnexin (CNX) was the only one factor, which belonged to both groups, suggesting that CNX might play a key role in arginine-induced insulin secretion in ER.

Fenugreek with reduced bitterness prevents diet-induced metabolic disorders in rats

BackgroundVarious therapeutic effects of fenugreek (Trigonella foenum-graecum L.) on metabolic disorders have been reported. However, the bitterness of fenugreek makes it hard for humans to eat sufficient doses of it for achieving therapeutic effects. Fenugreek contains bitter saponins such as protodioscin. Fenugreek with reduced bitterness (FRB) is prepared by treating fenugreek with beta-glucosidase. This study has been undertaken to evaluate the effects of FRB on metabolic disorders in rats.MethodsForty Sprague–Dawley rats were fed with high-fat high-sucrose (HFS) diet for 12 week to induce mild glucose and lipid disorders. Afterwards, the rats were divided into 5 groups. In the experiment 1, each group (n = 8) was fed with HFS, or HFS containing 2.4% fenugreek, or HFS containing 1.2%, 2.4% and 4.8% FRB, respectively, for 12 week. In the experiment 2, we examined the effects of lower doses of FRB (0.12%, 0.24% and 1.2%) under the same protocol (n = 7 in each groups).ResultsIn the experiment 1, FRB dose-dependently reduced food intake, body weight gain, epididymal white adipose tissue (EWAT) and soleus muscle weight. FRB also lowered plasma and hepatic lipid levels and increased fecal lipid levels, both dose-dependently. The Plasma total cholesterol levels (mmol/L) in the three FRB and Ctrl groups were 1.58 ± 0.09, 1.45 ± 0.05*, 1.29 ± 0.07* and 2.00 ± 0.18, respectively (*; P < 0.05 vs. Ctrl). The Hepatic total cholesterol levels (mmol/g liver) were 0.116 ± 0.011, 0.112 ± 0.006, 0.099 ± 0.007* and 0.144 ± 0.012, respectively (*; P < 0.05 vs. Ctrl). The calculated homeostasis model assessment as an index of insulin resistance (HOMA-IR) indicated 0.52 ± 0.04*, 0.47 ± 0.06*, 0.45 ± 0.05* and 1.10 ± 0.16, respectively (*; P < 0.05 vs. Ctrl). None of the FRB groups showed any adverse effect on the liver, kidney or hematological functions. In the experiment 2, no significant difference of food intake was observed, while the 1.2% FRB group alone showed nearly the same effects on glucose and lipid metabolism as in the experiment 1.ConclusionsThus we have demonstrated that FRB (1.2 ~ 4.8%) prevents diet-induced metabolic disorders such as insulin resistance, dyslipidemia and fatty liver.