Glucose-induced sympathetic activation in obesity-prone and resistant rats

Half of the 3-month-old male Sprague-Dawley rats fed a diet enriched in calories, sucrose and fat (CM diet) for 3 months developed diet-induced obesity (DIO) while the remainder were diet resistant (DR), gaining the same amount of weight as chow-fed controls. DIO was associated with basal hyperinsulinemia and 196 percent heavier retroperitoneal fat pads than DR and chow-fed rats. Intravenous glucose infusion (lg/kg) also produced greater insulin release in DIO rats associated with a 25 percent reduction in glucose disposal rates; areas under the insulin curve were 273 and 51 percent higher than chow-fed and DR rats, respectively. DR rats, on the other hand, showed normal glucose disposal rates but increased insulin release to a glucose load (148 percent greater area under the curve than chow-fed rats). Glucose infusion produced activation of the sympathetic nervous system with release of norepinephrine (NE) into the plasma in chow-fed and DIO but not DR rats which had 40-50 percent lower areas under the NE curve. Also, the areas under the NE curve correlated with body weight gain (r = 0.632; P = 0.040) and retroperitoneal fat pad weight (r = 0.707; P = 0.030) in DR and DIO rats suggesting that glucose-induced sympathetic activation was in some way related to an underlying mechanism of body weight regulation in Sprague-Dawley rats.     

Intracarotid glucose induced norepinephrine response and the development of diet induced obesity.

Intracarotid glucose infusions cause increased plasma norepinephrine (NE) levels in some rats. This is used as an index of sympathetic activation. Similar increases in plasma NE levels are produced by intravenous glucose injections and these levels correlate positively with the amount of weight gained by adult rats when they are subsequently fed a diet enriched in calories, sucrose and fat (condensed milk (CM) diet) for three months. Thus, rats prone to develop diet induced obesity (DIO) on the CM diet have greater intravenous glucose induced NE responses than those which are diet resistant (DR). To test the hypothesis that this relationship is mediated by the brain, 17 chow fed, adult male Sprague-Dawley rats were infused for 60 min with intracarotid glucose at 4 mg/kg/min and blood samples were obtained for plasma catecholamines, insulin and glucose. They were then placed on the CM diet for three months. After three months on the CM diet, there was a wide variability in body weight gain and the weights of retroperitoneal fat pads, an indirect measure of carcass adiposity. For all 17 rats, there was a significant correlation between both body weight gain (r = 0.685, P = 0.002) and retroperitoneal fat pad weights (r = 0.590, P = 0.013) with the levels of plasma NE reached 45-60 min into the preceding intracarotid glucose infusions. For the six lowest and six highest glucose induced NE responders, the correlation between NE response and body weight gain on CM diet was r = 0.944 (P = 0.0001). Plasma epinephrine, insulin and glucose levels were unchanged during such infusions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential effects of exercise on body weight gain and adiposity in obesity-prone and -resistant rats

OBJECTIVE: To determine the effect of exercise on weight gain and adiposity in obesity-prone and -resistant rats. DESIGN: Body weight gain, fat pad weights, food intake, plasma leptin and insulin levels were assessed in outbred male Sprague-Dawley rats, which remained sedentary or were given unrestricted access to running wheels either before or after they developed diet-induced obesity (DIO) or diet-resistance (DR) on a high energy (HE; 31% fat) diet. RESULTS: When fed a low fat (4.5%) chow diet, rats which would later develop DIO (n=6) after 3 weeks on HE diet ran the same amount as DR rats (n=6). Other rats were first made DIO (n=12) or DR (n=12) after 10 weeks on HE diet and then either kept sedentary or given running wheels for 4 weeks on HE diet. DIO and DR rats ran comparable amounts but only the DIO rats reduced their body weight gain, fat pad relative to body weights and plasma leptin levels significantly, compared to their sedentary controls. Exercise had no effect on food intake in either DIO or DR rats but reduced feed efficiency (weight gain/caloric intake) in both. CONCLUSION: Although DIO and DR rats ran similar amounts, the greater reduction in body weight gain and adiposity of exercising DIO rats suggests that they are more sensitive to some metabolic or physiologic system that prevents them from increasing their intake sufficiently to compensate for their net reduction in energy stores.     

Development of dietary obesity in rats: influence of amount and composition of dietary fat.

This study was conducted to examine long-term effects of amount and type of dietary fat on body weight and body composition. Adult male Wistar rats were fed high fat (HF; 60% of calories) or low fat (LF; 20% of calories) diets for 28 weeks. Half of the rats in each condition received diets with saturated fat (lard) (S) and the remainder received diets with polyunsaturated fat (corn oil) (U). From 28-39 weeks, HF rats were switched to LF diets (fat type remained constant). From 40-50 weeks, previously HF fed rats were weight-matched to rats in the LF fed groups. HF rats became fatter than LF rats during weeks 1-28 and remained heavier and fatter from weeks 28-39. During weeks 1-28, type of dietary fat had no effect on total body fat in either HF or LF rats, but during period 2 (weeks 28-39), U rats were heavier and fatter than S rats. There was some indication that U diets were associated with greater accumulation of fat in subcutaneous adipose tissue depots than S diets. From 40-50 weeks, rats previously fed the HF diet required less food to maintain their body weight than did LF diet rats. In summary, these results suggest that although both amount and type of dietary fat can affect body weight and body composition, the effects of the type of fat are less than those of amount of dietary fat.     

Nutritional effects on the lifespan of Syrian hamsters

Syrian hamsters were fed one of nine semipurified diets composed of three casein levels (9, 18, and 36 g/385 Kcal), with each of three corn oil levels (4.5, 9.0, and 18.0 g/385 Kcal). These diets were given either for five weeks and were followed by control diet (18 g casein and 9 g corn oil/385 Kcal) or control diet was fed for the first five weeks and was followed by the nine diets. Calorie consumption, maximum body weight and length of growth period and of life are reported. Calorie consumption was directly related to dietary fat levels. Maximum body weights increased with increasing dietary fat and protein when the various diets were fed during weeks 1–5. This result was not due to a conditioning of the animals fed high-fat or high-protein levels during weeks 1–5 to consume more calories after week 5, since after this time consumption was the same in all groups fed the control diet. When diets were fed from week 6 body weight increased in both sexes with increased dietary fat; however, higher dietary protein increased female and decreased male maximum body weight. Males took longer to reach these maximum weights than females, and were not affected by receiving the various diets during weeks 1–5. However, when diets were fed from week 6 until death, the growth period increased with higher dietary fat or protein. Male hamsters survived longer than females with each experimental treatment. Animals fed low-fat, low-protein diet or high-fat, high-protein diet during the first 5 weeks of the study survived longest. When diets were fed from 6 weeks until death, survival increased as dietary fat rose for both sexes. In contrast, survival improved as dietary protein rose for females or decreased for males. These studies establish a basis for further investigations on the link between nutrition and longevity in the Syrian hamster.     

Influence of a palatable,high-fat diet,and exercise training on the high-density lipoprotein to total cholesterol ratio in the rat

The influence of a palatable, high-energy diet, and exercise training on the levels of serum total cholesterol (CHOL) and CHOL carried by high-density lipoproteins (HDL CHOL) was investigated. Female rats were fed either a laboratory chow or a diet made of palatable food items containing a high level of fat. The animals receiving the latter were divided into groups fed either ad libitum, or pair-fed, on a calorie basis, with the chow-fed animals. Half of the animals were submitted to a swimming program for 4 wk. Body weight, total and HDL CHOL were measured at the end of the treatments. Exercise-trained rats ingested the same amount of calories as their sedentary counterparts, while the animals fed with high-energy diet ate almost twice as many calories as the chow-fed groups. The sedentary animals fed the palatable diet had higher body weights than the chow-fed animals, and exercise prevented this weight increase. Exercise did not have any significant effect on serum total CHOL, but increased significantly the HDL/total CHOL ratio by 15% in the chow-fed animals. The palatable diet increased total CHOL, and decreased the HDL/total CHOL ratio in sedentary animals, whereas the ratio in their trained counterparts was comparable to that of the sedentary chow-fed group. Exercise can thus prevent both weight gain and a decrease in HDL/total CHOL ratio produced by a palatable, high-energy diet in the female rat.     

Effects of long-term high-sucrose and dexamethasone on fat depots, liver fat, and lipid fuel fluxes through the retroperitoneal adipose tissue and splanchnic area in rats

In affluent societies high caloric intake and chronic stress are currently associated with upper body fat. We investigated the effects of a high-sucrose (S) diet and dexamethasone (DEX) on fat depots (experiment 1) and lipid fuel fluxes (experiment 2) in male Wistar rats. In experiment 1, a liquid diet of commercial powdered milk containing 31% calories as carbohydrate or an isocaloric S diet (80% calories as carbohydrate) was offered to male rats. One half of the rats on each diet received a daily dose of 3 microg DEX in their diet. Intake was measured daily and body weight 3 times a week. Rats were killed after 7 weeks, and fat depot weights and carcass lipid were determined. In a second experiment, other rats received only the S diet with or without DEX. After 7 weeks, under pentobarbital anesthesia, arterial, portal, and iliolumbar vein blood was drawn, and the liver was extracted. Plasma concentration of triacylglycerides (TAG), nonesterified fatty acids (NEFA), glycerol (GOL), and lactate (L) and liver TAG were measured. Rats on the S diet ingested less and gained less weight. DEX treatment significantly reduced body weight gain. All fat depots as percentage of body weight were increased only in the S-DEX group. The S-DEX group had more liver TAG and less arterial NEFA and GOL than the S group. TAG determinations showed unexpected results: portal levels in the S-DEX group and iliolumbar levels in both groups were significantly higher than in the arterial plasma. This fact, together with high NEFA/GOL ratios in these veins, may signify incomplete TAG hydrolysis by lipoprotein lipase. L levels were higher in the S-DEX group and higher in arterial versus venous blood in both groups, indicating L uptake both in the splanchnic area and the retroperitoneal fat. These results show that, in rats, a long-term high-sucrose diet has peculiar effects on L turnover, and when associated with DEX, it also increases fat depots, induces liver steatosis, and, presumably, inhibits complete hydrolysis of TAG by lipoprotein lipase (LPL).     

Increased brain 3H-paraminoclonidine (alpha 2-adrenoceptor) binding associated with perpetuation of diet-induced obesity in rats

Brain alpha-adrenoceptor (alpha-AR) binding was examined as a possible explanation for the persistence of diet-induced obesity (DIO) or resistance (DR) in rats after they were returned to chow from a high-energy, fat and sucrose diet (CM diet). Adult Sprague-Dawley rats (n = 28) were fed the CM diet for 12 weeks. Those that gained more weight than chow-fed controls were classified as DIO and those that gained the same weight as controls were called DR. The 10 heaviest DIO and 8 lightest DR rats were then placed on chow for an additional 14 weeks. After the entire 26-week period, the body weights of DIO rats were still 21 per cent greater and those of the DR rats were 9 per cent less than 7 chow-fed controls. DIO retroperitoneal fat pads were also 62 per cent heavier while DR pads were equal to controls. Plasma insulin and glucose levels were comparable in all 3 groups. Receptor autoradiographic studies of brain alpha 1-AR (3H prazosin; PRZ) and alpha 2-AR (3H-paraminoclonidine; PAC) adrenoceptor binding were carried out using these animals at the end of 26 weeks. Binding to alpha 1-AR was comparable in all groups but alpha 2-AR binding was 47-103 per cent higher in DIO compared to DR and chow-fed controls in 14 of 17 brain areas assessed. These included the dorsomedial, ventromedial and paraventricular hypothalamic n. and all amygdalar areas. Such widespread differences in alpha 2-AR binding in rats fed the same diet but of differing body weights suggest that alpha 2-AR binding is a marker for differences in body weight regulation and may be important in the control of the differences in weight gain.     

A low glycaemic diet improves oral glucose tolerance but has no effect on β-cell function in C57BL/6J mice

Aim: Clinical studies have suggested a role for dietary glycaemic index (GI) in body weight regulation and diabetes risk. Here, we investigated the long‐term metabolic effects of low and high glycaemic diets using the C57BL/6J mouse model. Methods: Female C57BL/6J mice were fed low or high glycaemic starch in either low‐fat or medium‐fat diets for 22 weeks. Oral and intravenous glucose tolerance tests were performed to investigate the effect of the experimental diets on glucose tolerance and insulin resistance. Results: In this study, a high glycaemic diet resulted in impaired oral glucose tolerance compared to a low glycaemic diet. This effect was more pronounced in the group fed a medium‐fat diet, suggesting that a lower dietary fat content ameliorates the negative effect of a high glycaemic diet. No effect on body weight or body fat content was observed in either a low‐fat diet or a medium‐fat diet. Static incubation of isolated islets did not show any differences in basal (3.3 mM glucose) or glucose‐stimulated (8.6 and 16.7 mM glucose) insulin secretion between mice fed a low or high glycaemic diet. Conclusion: Together, our data suggest that the impaired glucose tolerance seen after a high glycaemic diet is not explained by altered β‐cell function.     

Cardiovascular function in a rat model of diet-induced obesity

The obesity-prone/obesity-resistant rat model has been used to study mechanisms responsible for obesity-related abnormalities in renal function and blood pressure, but whether this model exhibits cardiac dysfunction has not been determined. We tested the hypothesis that obesity-prone rats would display cardiovascular abnormalities seen in other diet-induced obese models (ie, hypertension, tachycardia, left ventricular hypertrophy, increased collagen deposition, reduced cardiac contractility, and increased end diastolic pressure). Male Sprague-Dawley rats were fed a control diet or a moderate fat diet containing 32% kcal as fat while hemodynamics were continuously monitored using telemetry. After 12 weeks, obesity-prone rats were significantly heavier and had greater body fat compared with obesity-resistant rats and controls, but daily (20 hours/d) averages and diurnal rhythms of blood pressure and heart rate did not differ among groups. Echocardiographic indices of cardiac structure and function, histological evidence of cardiac collagen, and directly measured heart weights did not differ among groups. Peak left ventricular pressure, end diastolic pressure, +dP/dt, and -dP/dt were also not significantly different among groups. Plasma cholesterol and hepatic cholesterol were significantly higher in obesity-prone rats compared with obesity-resistant rats and controls; hepatic triglycerides were higher in obesity-prone rats compared with controls (P< or =0.05). Leptin was significantly higher in obesity-prone rats compared with controls and across all groups was significantly correlated with body fat (P< or =0.05). These results suggest that 12 weeks of a moderate fat diet in the obesity-prone/obesity-resistant rat model induced lipid and endocrine abnormalities typical of obesity but was not sufficient to cause significant cardiac abnormalities.     

Comparison of 4 diets of varying glycemic load on weight loss and cardiovascular risk reduction in overweight and obese young adults: a randomized controlled trial

BACKGROUND: Despite the popularity of low-glycemic index (GI) and high-protein diets, to our knowledge no randomized, controlled trials have systematically compared their relative effects on weight loss and cardiovascular risk. METHODS: A total of 129 overweight or obese young adults (body mass index, > or =25 [calculated as weight in kilograms divided by the square of height in meters]) were assigned to 1 of 4 reduced-fat, high-fiber diets for 12 weeks. Diets 1 and 2 were high carbohydrate (55% of total energy intake), with high and low GIs, respectively; diets 3 and 4 were high protein (25% of total energy intake), with high and low GIs, respectively. The glycemic load was highest in diet 1 and lowest in diet 4. Changes in weight, body composition, and blood chemistry profile were studied. RESULTS: While all groups lost a similar mean +/- SE percentage of weight (diet 1, -4.2% +/- 0.6%; diet 2, -5.5% +/- 0.5%; diet 3, -6.2% +/- 0.4%; and diet 4, -4.8% +/- 0.7%; P = .09), the proportion of subjects in each group who lost 5% or more of body weight varied significantly by diet (diet 1, 31%; diet 2, 56%; diet 3, 66%; and diet 4, 33%; P = .01). Women on diets 2 and 3 lost approximately 80% more fat mass (-4.5 +/- 0.5 [mean +/- SE] kg and -4.6 +/- 0.5 kg) than those on diet 1 (-2.5 +/- 0.5 kg; P = .007). Mean +/- SE low-density-lipoprotein cholesterol levels declined significantly in the diet 2 group (-6.6 +/- 3.9 mg/dL [-0.17 +/- 0.10 mmol/L]) but increased in the diet 3 group (+10.0 +/- 3.9 mg/dL [+0.26 +/- 0.10 mmol/L]; P = .02). Goals for energy distribution were not achieved exactly: both carbohydrate groups ate less fat, and the diet 2 group ate more fiber. CONCLUSION: Both high-protein and low-GI regimens increase body fat loss, but cardiovascular risk reduction is optimized by a high-carbohydrate, low-GI diet.     

Western-type diets induce insulin resistance and hyperinsulinemia in LDL receptor-deficient mice but do not increase aortic atherosclerosis compared with normoinsulinemic mice in which similar plasma cholesterol levels are achieved by a fructose-rich diet.

The role of insulin resistance (IR) in atherogenesis is poorly understood, in part because of a lack of appropriate animal models. We assumed that fructose-fed LDL receptor-deficient (LDLR-/-) mice might be a model of IR and atherosclerosis because (1) fructose feeding induces hyperinsulinemia and IR in rats; (2) a preliminary experiment showed that fructose feeding markedly increases plasma cholesterol levels in LDLR-/- mice; and (3) hypercholesterolemic LDLR-/- mice develop extensive atherosclerosis. To test whether IR could be induced in LDLR-/- mice, 3 groups of male mice were fed a fructose-rich diet (60% of total calories; n=16), a fat-enriched (Western) diet intended to yield the same plasma cholesterol levels (n=18), or regular chow (n=7) for approximately 5.5 months. The average cholesterol levels of both hypercholesterolemic groups were similar (849+/-268 versus 964+/-234 mg/dL) and much higher than in the chow-fed group (249+/-21 mg/dL). Final body weights in the Western diet group were higher (39+/-6.2 g) than in the fructose- (27.8+/-2.7 g) or chow-fed (26.7+/-3.8 g) groups. Contrary to expectation, IR was induced in mice fed the Western diet, but not in fructose-fed mice. The Western diet group had higher average glucose levels (187+/-16 versus 159+/-12 mg/dL) and 4.5-fold higher plasma insulin levels. Surprisingly, the non-insulin-resistant, fructose-fed mice had significantly more atherosclerosis than the insulin-resistant mice fed Western diet (11.8+/-2.9% versus 7.8+/-2. 5% of aortic surface; P<0.01). These results suggest that (1) fructose-enriched diets do not induce IR in LDLR-/- mice; (2) the Western diets commonly used in LDLR-/- mice may not only induce atherosclerosis, but also IR, potentially complicating the interpretation of results; and (3) IR and hyperinsulinemia do not enhance atherosclerosis in LDLR-/- mice, at least under conditions of very high plasma cholesterol levels. The fact that various levels of hypercholesterolemia can be induced in LDLR-/- mice by fat-enriched diets and that such diets induce IR and hyperinsulinemia suggest that LDLR-/- mice may be used as models to elucidate the effect of IR on atherosclerosis, eg, by feeding them Western diets with or without insulin-sensitizing agents.     

High-fat diet feeding reduces the diurnal variation of plasma leptin concentration in rats

To investigate the response of plasma leptin and its diurnal variation to graded levels of dietary fat intake, adult (486.8+/-10.8 g), male rats (N = 52) were fed diets containing 12%, 28%, 44%, and 60% fat for 4 weeks. The body weight gain and abdominal fat pad weight were higher (P < .05) in groups fed diets containing 44% and 60% fat compared with the two diets containing less fat. There were no significant differences in terms of body weight or fat pad weight between animals fed the two diets with higher fat content or between animals fed the two lower-fat diets. Twenty-four-hour energy expenditure was not different among the dietary fat groups. After 3 days on the experimental diets, plasma leptin increased (P < .03) in all dietary groups. The increases in leptin in animals fed 12% and 28% fat diets occurred primarily in the morning. In contrast, in groups fed the two diets containing higher fat content, leptin levels increased mainly in the afternoon. As a result, the daily variation in leptin increased (P < .05) in the two groups fed lower-fat diets, but decreased (P < .04) in animals fed the two higher-fat diets. These data demonstrate that short-term high-fat diet feeding abolished the diurnal fluctuation of plasma leptin levels, which may prevent proper leptin function and eventually contribute to the development of obesity.     

Effects of cationic hydroxyethyl cellulose on glucose metabolism and obesity in a diet-induced obesity mouse model

Background: To investigate the effect of a new soluble fiber, namely cationic hydroxyethyl cellulose (cHEC), on weight loss and metabolic disorders associated with obesity using a high‐fat diet‐induced obese mouse model. Methods: Obese male C57BL/6J (B6) mice were fed high‐fat (60% kcal) diets supplemented with cHEC for 5 weeks. Body weight, energy intake, mesenteric adipose and liver weights, plasma cholesterol, plasma insulin, glucose, adiponectin, and leptin were assessed to determine the effects of cHEC. Hepatic and fecal lipids were also analyzed to investigate the effect of cHEC on lipid absorption and metabolism. Results: Supplementation of the high‐fat diet with cHEC resulted in significant weight loss in obese mice. In addition, significant decreases were seen in mesenteric adipose and liver weights, as well as concentrations of plasma cholesterol and hepatic lipids. A significant improvement in glucose homeostasis, insulin sensitivity, and leptin concentrations were observed at 4% cHEC. Moreover, increases in fecal excretion of total bile acids, sterols, and fats indicated altered fat absorption when cHEC was supplemented in the diet. Conclusions: We have shown in the present study that cHEC reduces body weight, improves insulin sensitivity, and prevents the development of metabolic syndrome. Furthermore, the effects of cHEC on glucose and lipid homeostasis in B6 mice are mediated by improvements in leptin sensitivity resulting from reduced fat absorption.     

Development of high fat diet-induced obesity and leptin resistance in C57Bl/6J mice

OBJECTIVE: To investigate the development of high fat diet-induced obesity and leptin resistance. DESIGN: Two experiments were carried out in this study. Firstly, we fed the mice with a high- or low-fat diet for up to 19 weeks to examine a progressive development of high fat diet-induced obesity. Secondly, we examined peripheral and central exogenous leptin sensitivity in mice fed high- or low-fat diets for 1, 8 or 19 weeks. SUBJECTS: A total of 168 C57BL/6J mice (3 weeks old) were used in this study. MEASUREMENTS: In the first experiment, we measured the body weight, energy intake, adipose tissue mass, tibia bone length, and plasma leptin in mice fed either a high- or low-fat diet for 1, 8, 15 and 19 weeks. In the second experiment, body weight change and cumulative energy intake were measured at 6 h intervals for 72 h after leptin injection in mice fed a high- or low-fat diet for 1, 8 or 19 weeks. RESULTS: The results from the first experiment suggested that the development of high fat diet-induced obesity in mice could be divided into early, middle and late stages. Compared with the mice fed a low-fat diet, the mice fed a high-fat diet showed a gradually increased body weight (+5.2%), fat storage (epididymal plus perirenal; +6.7%) and plasma leptin (+18%) at 1 week; +11.4%, +68.1%, and +223%, respectively, at 8 weeks; and +30.5%, +141%, and +458%, respectively, at 19 weeks. Energy intake of high fat diet-fed mice was equal to that of low fat diet-fed controls for the first 3 weeks; it fell below control levels over the next 5 week period, but began to increase gradually after 8 weeks of high-fat diet feeding and then increased dramatically from 15 weeks to be 14% higher than that of controls after 19 weeks. The results from our second experiment showed that: (1) after 1 week of feeding, the mice fed a high-fat diet were sensitive to a 2 microg/g (body weight) intraperitoneal (i. p.) injection of leptin, with no differences in body weight change or cumulative energy intake post-injection; (2) after 8 weeks of feeding, the mice fed a high-fat diet were insensitive to 2 microg/g (body weight) i.p. leptin, but were sensitive to a 0.1 microg intracerebroventricular (i.c.v.) injection of leptin; (3) after 19 weeks of feeding, the mice fed a high-fat diet were insensitive to 0. 1 microg i.c.v. leptin, but were sensitive to a high dose of 2 microg i.c.v. leptin. CONCLUSIONS: The present study demonstrated that the development of high fat diet-induced obesity (19 weeks) in C57 B1/6J mice could be divided into three stages: (1) an early stage in response to high-fat diet that mice were sensitive to exogenous leptin; (2) a reduced food intake stage when mice had an increase in leptin production and still retained central leptin sensitivity; and (3) an increased food intake stage, accompanied by a reduction of central leptin sensitivity.     

体重下降对肥胖人群血脂的影响

目的:评价控制体重和体重指数对血脂的影响。方法:55例体重超标、高血脂、愿意降低体重的自愿参加者,在26周内通过控制饮食和锻炼降低体重。结果:研究过程中所有患者通过适量的体育锻炼和节食后,其体重和体重指数,以及血脂均有下降。在男性患者中,胆固醇下降水平与体重和体重指数下降密切相关。女性患者的胆固醇降低较男性患者更多,体重和体重指数下降较男性患者少,组间有显著性差异。结论:超重者通过锻炼身体和合理节食可以明显降低体重、体重指数和血脂水平。     

Improvement of insulin sensitivity after peroxisome proliferator-activated receptor-alpha agonist treatment is accompanied by paradoxical increase of circulating resistin levels

We studied the effect of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) activation on serum concentrations and tissue expression of resistin, adiponectin, and adiponectin receptor-1 and -2 (AdipoR1 and AdipoR2) mRNA in normal mice and mice with insulin resistance induced by lipogenic, simple-carbohydrate diet (LD). Sixteen weeks of LD feeding induced obesity with liver steatosis and increased insulin levels but did not significantly affect circulating adiponectin or resistin. Treatment with PPAR-alpha agonist fenofibrate decreased body weight and fat pad weight and ameliorated liver steatosis in LD-fed mice with concomitant reduction in blood glucose, free fatty acid, triglyceride, serum insulin levels, and homeostasis model assessment index values. Euglycemic-hyperinsulinemic clamp demonstrated the development of whole-body and liver insulin resistance in LD-fed mice, which were both normalized by fenofibrate. Fenofibrate treatment markedly increased circulating resistin levels on both diets and adiponectin levels in chow-fed mice only. Fat adiponectin mRNA expression was not affected by fenofibrate treatment. Resistin mRNA expression increased in subcutaneous but not gonadal fat after fenofibrate treatment. In addition to fat, a significant amount of adiponectin mRNA was also expressed in the muscle. This expression markedly increased after fenofibrate treatment in chow- but not in LD-fed mice. Adipose tissue expression of AdipoR1 mRNA was significantly reduced in LD-fed mice and increased after fenofibrate treatment. In conclusion, PPAR-alpha activation ameliorated the development of insulin resistance in LD-fed mice despite a major increase in serum resistin levels. This effect could be partially explained by increased AdipoR1 expression in adipose tissue after fenofibrate treatment.     

Effect of high-fat diet on body composition and hormone responses to glucose tolerance tests

To determine potential hormonal mediators of the effect of high-fat diets on the development of insulin resistance, blood leptin, growth hormone (GH), glucose, and insulin responses to a 2 g/kg BW oral glucose challenge were evaluated in weanling female Sprague Dawley rats that were randomly assigned to a high-fat (HF, 39% of calories, 20% fat by weight; n = 10) and moderate-fat (MF, 22% of calories, 10% fat by weight; n = 10) diets. Oral glucose challenges were administered following 5, 7, and 9 wk on the feeding trial. Animals were provided diet in excess of their requirements for growth. Body mass analysis was conducted by dual X-ray absorptiometry (DXA) on the 6th, 8th, and 10th weeks of the trial. HF animals gained more weight after 7 wk, had greater body fat than the MF animals, and similar glucose responses to the oral glucose challenges. HF rats secreted more insulin and leptin compared to MF animals. Lean body mass and serum GH and IGF-I concentrations were not different between the groups. Results of this study demonstrate that leptin but not GH or IGF-I is involved in the development of insulin resistance in growing rats as a result of excess energy intake in the form of dietary fat.     

Effect of a culturally sensitive cholesterol lowering diet program on lipid and lipoproteins,body weight,nutrient intakes,and quality of life in patients with systemic lupus erythematosus

OBJECTIVE: To evaluate the effect of a culturally sensitive cholesterol lowering diet program on lipid and lipoproteins, body weight, nutrient intakes, and quality of life (QOL) in patients with systemic lupus erythematosus (SLE). METHOD: Seventeen patients with SLE were randomized to a Step 2 diet intervention group or a control group for 12 weeks. The diet intervention was made up of weekly group sessions during the first 6 weeks followed by telephone counseling every 2 weeks for the last 6 weeks. Data on fasting lipid and lipoproteins, body weight, food intake (3 day food record), and QOL were collected at baseline, 6 weeks, and 12 weeks. Program acceptability was assessed in the diet group at 6 weeks. RESULTS: The intervention was found to be highly acceptable and culturally sensitive. The changes in nutrient intakes at 6 and 12 weeks in the diet group were -49% and -33%, respectively, for cholesterol, -44% and -32%, respectively, for percentage calories from fat, and -46% and -32%, respectively, for percentage calories from saturated fat. The corresponding figures in the control group were +22% and -8% for cholesterol, +9% and +6% for percentage calories from fat, and +5% and +7% for percentage calories from saturated fat. The treatment by time interaction was significant for all the dietary variables (p = 0.0003 to 0.02). QOL was reported to improve by 15-17% in the diet group and decrease by 4-6% in the control group, and the treatment by time interaction was significant (p = 0.05). The changes in the physiological variables at 6 and 12 weeks in the diet group were -10% and -6%, respectively, for total cholesterol, -10% and -2%, respectively, for low density lipoprotein (LDL) cholesterol, -11% and -4%, respectively, for high density lipoprotein (HDL) cholesterol, -25% and -34%, respectively, for very low density lipoprotein (VLDL) cholesterol, -8% and -24%, respectively, for triglycerides, and -2% and -5%, respectively, for body weight. The corresponding figures in the control group were -5% and -3% for total cholesterol, -6% and -5% for LDL cholesterol, 0% and +12% for HDL cholesterol, +4% and -8% for VLDL cholesterol, -6% and -15% for triglycerides, and -5% and -6% for body weight. The treatment by time interaction was significant for HDL cholesterol (p = 0.04). A significant reduction was seen in the diet group for total cholesterol at 6 and 12 weeks, LDL and HDL cholesterol at 6 weeks, and body weight at 12 weeks (p = 0.0002 to 0.01). CONCLUSION: This culturally sensitive cholesterol reducing diet program was highly accepted and effective in changing the diet and QOL of patients with SLE. The effect on serum lipids, lipoproteins, and body weight, however, was modest. A larger randomized study with a longer intervention period is necessary to test the effectiveness of a cholesterol-lowering diet on lipids and lipoproteins in patients with SLE.     

Randomized comparison of reduced fat and reduced carbohydrate hypocaloric diets on intrahepatic fat in overweight and obese human subjects

Obesity-related hepatic steatosis is a major risk factor for metabolic and cardiovascular disease. Fat reduced hypocaloric diets are able to relieve the liver from ectopically stored lipids. We hypothesized that the widely used low carbohydrate hypocaloric diets are similarly effective in this regard. A total of 170 overweight and obese, otherwise healthy subjects were randomized to either reduced carbohydrate (n = 84) or reduced fat (n = 86), total energy restricted diet (-30% of energy intake before diet) for 6 months. Body composition was estimated by bioimpedance analyses and abdominal fat distribution by magnetic resonance tomography. Subjects were also submitted to fat spectroscopy of liver and oral glucose tolerance testing. In all, 102 subjects completed the diet intervention with measurements of intrahepatic lipid content. Both hypocaloric diets decreased body weight, total body fat, visceral fat, and intrahepatic lipid content. Subjects with high baseline intrahepatic lipids (>5.56%) lost ≈7-fold more intrahepatic lipids compared with those with low baseline values (<5.56%) irrespective of diet composition. In contrast, changes in visceral fat mass and insulin sensitivity were similar between subgroups, with low and high baseline intrahepatic lipids. CONCLUSION: A prolonged hypocaloric diet low in carbohydrates and high in fat has the same beneficial effects on intrahepatic lipid accumulation as the traditional low-fat hypocaloric diet. The decrease in intrahepatic lipids appears to be independent of visceral fat loss and is not tightly coupled with changes in whole body insulin sensitivity during 6 months of an energy restricted diet.