Inherent capacity for lipogenesis or dietary fat retention is not increased in obesity-prone rats

Obesity results from positive energy balance and, perhaps, abnormalities in lipid and glycogen metabolism. The purpose of this study was to determine whether differences in lipogenesis, retention of dietary fat, and/or glycogenesis influenced susceptibility to dietary obesity. After 1 wk of free access to a high-fat diet (HFD; 45% fat by energy) rats were separated on the basis of 1 wk body weight gain into obesity-prone (OP; > or =48 g) or obesity-resistant groups (OR; < or =40 g). Rats were either studied at this time (OR1, OP1) or continued on the HFD for an additional 4 wk (OR5, OP5). Weight gain and energy intake were greater (P < or = 0.05) in OP vs. OR at both 1 (53 +/- 2 vs. 34 +/- 1 g; 892 +/- 27 vs. 755 +/- 14 kcal) and 5 (208 +/- 7 vs. 170 +/- 7 g; 4,484 +/- 82 vs. 4,008 +/- 72 kcal) wk, respectively. Rats were injected with (3)H(2)O and were either provided free access to an HFD meal containing labeled fatty acids (fed; n = 10 or 11/group) or were fasted (n = 10/group) overnight. The amount of food or (14)C tracer eaten overnight was equivalent between OP and OR rats. In liver, the fraction of (3)H retained in glycogen or lipid was not significantly different between OR and OP groups. Retention of dietary fat in the liver was not increased in OP rats. In adipose tissue, retention of (3)H was approximately 49% greater (P < or = 0.05) in OP1 vs. OR1 and approximately 30% greater in OP5 vs. OR5, but retention of dietary fat was not elevated in OP vs. OR. At the same time, fat pad weight (sum of epididymal, retroperitoneal, mesenteric) was 49% greater in OP1 rats vs. OR1 rats and 65% greater in OP5 vs. OR5 rats (P < or = 0.05). Thus a greater capacity for lipogenesis or retention of dietary fat does not appear to be included in the OP phenotype. The characteristic increase in energy intake associated with OP rats appears to be necessary and critical to accelerated weight and fat gain.     

Fat oxidation, lipolysis, and free fatty acid cycling in obesity-prone and obesity-resistant rats

Defects in fat metabolism may contribute to the development of obesity, but what these defects are and where they occur in the feeding/fasting cycle are unknown. In the present study, basal fat metabolism was characterized using a high-fat diet (HFD)-induced model of obesity development. Male rats consumed a HFD (45% fat, 35% carbohydrate) ad libitum for either 1 or 5 wk (HFD1 or HFD5). After 1 wk on the HFD, rats were separated on the basis of body weight gain into obesity-prone (OP, > or =48 g) or obesity-resistant (OR, 相似文献   

Effect of sibutramine on regional fat pads and leptin levels in rats fed with three isocaloric diets

AIM: The aim of the study was to investigate: a) the differential effect of the three main macronutrients on food intake, fat depots and serum leptin levels and b) the impact of sibutramine on the above parameters in rats fed ad libitum with three isocaloric diets. METHODS: Three groups of male Wistar rats (n = 63) were fed with a high fat diet (HFD), a high carbohydrate diet (HCD) or a high protein diet (HPD) for 13 weeks. In the last three weeks, each group was divided into three subgroups and received sibutramine (S) either at 5 mg/kg or 10 mg/kg, or vehicle. Food intake was measured daily during the last week of the experiment; perirenal and epididymal fat and fat/lean ratio were calculated and serum leptin was assayed. RESULTS: HFD-fed rats demonstrated elevated food intake and higher regional fat depots. S at 10 mg/kg decreased food intake in the HFD and epididymal fat in the HCD group. S also reduced perirenal fat in the HCD and HPD groups. Leptin levels were higher in rats fed with either the HFD or the HPD compared to those fed with the HCD. Moreover, S at 10 mg/kg decreased serum leptin levels in the HPD group. CONCLUSIONS: Results suggest a preferential effect of S on perirenal visceral fat and support the view that body fat loss is greater when its administration is accompanied by a HCD diet. No effect of S on leptin levels was found, besides that expected as a result of the decrease in body fat.     

The Carbohydrate Sensitive Rat as a Model of Obesity

Background

Sensitivity to obesity is highly variable in humans, and rats fed a high fat diet (HFD) are used as a model of this inhomogeneity. Energy expenditure components (basal metabolism, thermic effect of feeding, activity) and variations in substrate partitioning are possible factors underlying the variability. Unfortunately, in rats as in humans, results have often been inconclusive and measurements usually made after obesity onset, obscuring if metabolism was a cause or consequence. Additionally, the role of high carbohydrate diet (HCD) has seldom been studied.

Methodology/Findings

Rats (n=24) were fed for 3 weeks on HCD and then 3 weeks on HFD. Body composition was tracked by MRI and compared to energy expenditure components measured prior to obesity. Results: 1) under HFD, as expected, by adiposity rats were variable enough to be separable into relatively fat resistant (FR) and sensitive (FS) groups, 2) under HCD, and again by adiposity, rats were also variable enough to be separable into carbohydrate resistant (CR) and sensitive (CS) groups, the normal body weight of CS rats hiding viscerally-biased fat accumulation, 3) HCD adiposity sensitivity was not related to that under HFD, and both HCD and HFD adiposity sensitivities were not related to energy expenditure components (BMR, TEF, activity cost), and 4) only carbohydrate to fat partitioning in response to an HCD test meal was related to HCD-induced adiposity.

Conclusions/Significance

The rat model of human obesity is based on substantial variance in adiposity gains under HFD (FR/FS model). Here, since we also found this phenomenon under HCD, where it was also linked to an identifiable metabolic difference, we should consider the existence of another model: the carbohydrate resistant (CR) or sensitive (CS) rat. This new model is potentially complementary to the FR/FS model due to relatively greater visceral fat accumulation on a low fat high carbohydrate diet.     

High‐fat Diet‐induced Ultradian Leptin and Insulin Hypersecretion are Absent in Obesity‐resistant Rats*

Objective: Sprague‐Dawley rats fed a high‐fat diet (HFD) are either obesity prone (OP) or obesity resistant (OR). We tested the hypothesis that differences in the ultradian rhythmic patterns of insulin and ghrelin in OP vs. OR rats promote obesity in OP rats. Research Methods and Procedures: Rats were fed regular chow or an HFD, and ultradian fluctuations in leptin, insulin, and ghrelin were analyzed in blood samples collected at 5‐minute intervals from intrajugular cannulae of freely moving rats. Results: Regular chow feeding resulted in a slow weight gain accompanied by small increases in insulin and leptin and a decrease in ghrelin discharge, with only the pulse amplitude significantly altered. Similar changes were observed in OR rats, despite HFD consumption. In contrast, OP rats exhibited a high rate of weight gain and marked hyperinsulinemia, hyperleptinemia, and hypoghrelinemia; amplitude was altered, but frequency was stable. In a short‐term experiment, HFD elicited similar secretory patterns of smaller magnitude even in the absence of weight gain. Discussion: We showed that three hormonal signals of disparate origin involved in energy homeostasis were secreted in discrete episodes, and only the pulse amplitude component was vulnerable to age and HFD consumption. Increases in insulin and leptin and decreases in ghrelin pulse amplitude caused by HFD were exaggerated in OP rats relative to OR rats and preceded the weight increase. These findings show that a distinct genetic predisposition in the endocrine organs of OR rats confers protection against high‐fat intake‐induced ultradian hypersecretion of obesity‐promoting hormonal signals.     

Dietary sphingomyelin attenuates hepatic steatosis and adipose tissue inflammation in high-fat-diet-induced obese mice

Western-type diets can induce obesity and related conditions such as dyslipidemia, insulin resistance and hepatic steatosis. We evaluated the effects of milk sphingomyelin (SM) and egg SM on diet-induced obesity, the development of hepatic steatosis and adipose inflammation in C57BL/6J mice fed a high-fat, cholesterol-enriched diet for 10 weeks. Mice were fed a low-fat diet (10% kcal from fat) (n=10), a high-fat diet (60% kcal from fat) (HFD, n=14) or a high-fat diet modified to contain either 0.1% (w/w) milk SM (n=14) or 0.1% (w/w) egg SM (n=14). After 10 weeks, egg SM ameliorated weight gain, hypercholesterolemia and hyperglycemia induced by HFD. Both egg SM and milk SM attenuated hepatic steatosis development, with significantly lower hepatic triglycerides (TGs) and cholesterol relative to HFD. This reduction in hepatic steatosis was stronger with egg SM supplementation relative to milk SM. Reductions in hepatic TGs observed with dietary SM were associated with lower hepatic mRNA expression of PPARγ-related genes: Scd1 and Pparg2 in both SM groups, and Cd36 and Fabp4 with egg SM. Egg SM and, to a lesser extent, milk SM reduced inflammation and markers of macrophage infiltration in adipose tissue. Egg SM also reduced skeletal muscle TG content compared to HFD. Overall, the current study provides evidence of dietary SM improving metabolic complications associated with diet-induced obesity in mice. Further research is warranted to understand the differences in bioactivity observed between egg and milk SM.     

Profiling of gender-specific rat plasma proteins associated with susceptibility or resistance to diet-induced obesity

Obesity-prone (OP) and obesity-resistant (OR) rats with different responses to development of obesity in spite of the same genetic background are useful animal models for searching for markers during the development of obesity. Here, we investigated whether plasma proteins of OP and OR rats may behave in a different way in males and females. We performed a comparative proteomic analysis using 2-DE combined with MALDI-TOF/MS on proteins from OP and OR male and female rats to discover gender-specific rat plasma proteins associated with susceptibility or resistance to diet-induced obesity. A total of 29 proteins showing differential expression between the groups were identified by MALDI-TOF/MS and database searches. These proteins were classified into 4 groups according to their regulation patterns in response to diet and gender. 22 proteins showed significant differences between OP and OR rats in males and/or females (Group I, II, and III) and 7 proteins exhibited only a high fat diet (HFD)-responsive difference in male or female rats (Group IV). In conclusion, the proteins negatively (ITIH3, FGG, TUBB5, and ZAG) or positively (Hp, ITIH4, and RBP) correlated with obesity found in this study could be used for selection of new targets for gender specific-medical treatment of obesity.     

High‐Fat Diet Feeding Elevates Skeletal Muscle Uncoupling Protein 3 Levels But Not Its Activity in Rats

Objective: The objective of this study is to test the impact of high‐fat diet (HFD) feeding on skeletal muscle (SM) uncoupling protein 3 (UCP3) expression and its association with mitochondrial ion permeability and whole‐body energy homeostasis. Research Methods and Procedures: Sprague–Dawley rats were fed ad libitum either a HFD (60% of energy from fat, n = 6) or a low‐fat diet (12% of energy from fat, n = 6) for 4 weeks. Twenty‐four‐hour energy expenditure was measured by indirect calorimetry in the last week of the dietary treatment. Blood samples were collected for plasma leptin and free fatty acid assays, and mitochondria were isolated from hindlimb SM for subsequent determinations of UCP3 levels and mitochondrial ion permeability. Results: Plasma leptin levels were higher in rats fed the HFD despite the same body weight in two groups. The same dietary treatment also rendered a 2‐fold increase in plasma free fatty acid and SM UCP3 protein levels (Western blot) compared with the group fed the low‐fat diet. However, the elevated UCP3 protein levels did not correlate with mitochondrial swelling rates, a measure of mitochondrial chloride, and proton permeability, or with 24‐hour energy expenditure. Discussion: The high correlation between the levels of plasma free fatty acid levels and SM UCP3 suggests that circulating free fatty acid may play an important role in UCP3 expression during the HFD feeding. However, the dissociation between the UCP3 protein levels and 24‐hour energy expenditure as well as mitochondrial ion permeability suggests that mitochondrial proton leak mediated by muscle UCP3 may not be a major contributor in energy balance in HFD feeding, and other regulatory mechanisms independent of gene regulation may be responsible for the control of UCP3‐mediated uncoupling activity.     

Neuropeptide Y Expression and Endogenous Leptin Concentrations in a Dietary Model of Obesity

LAUTERIO, THOMAS J., MICHAEL J. DAVIES, MARK DEANGELO, MICHAEL PEYSER, AND JAMES LEE. Neuropeptide Y expression and endogenous leptin concentrations in a dietary model of obesity. Obes Res. Objective: To determine how leptin concentrations and neuropeptide (NPY) are regulated in a model of dietary obesity in relation to relative growth (RG) and relative food consumption (RFC). Research Methods and Procedures: Sprague—Dawley rats were fed a moderately high-fat diet for 14 weeks over which time animals diverged into obesity-prone (OP) and obesity-resistant (OR) populations. RG rates and RFC were calculated weekly. Following the study, an adiposity index was calculated and arcuate nucleus (ARC) NPY expression was determined by in situ hybridization (ISH) or ribonuclease protection (RPA) assays. Results: Body weights were greater in OP rats after 2 weeks on the diet compared to OR rats and remained different throughout the study. RG and RFC were greater in OP rats compared to OR rats only during the first 2 weeks of the study. Leptin concentrations rose in both groups during the experiment, but the increase was greater in OP rats than in OR rats. Insulin changes paralleled those for leptin. ARC NPY mRNA expression was not different between OP and OR rats as measured by ISH and RPA. Discussion: Although NPY expression has been reported to be different initially in OP and OR rats, this difference dissipates following divergence of body weight. RFC and RG data suggest the initial NPY elevation may contribute to increased weight gain of OP rats during the first 2 weeks of the diet. Higher relative leptin concentrations in OP rats may be necessary to normalize differences in adiposity and apparent leptin and insulin resistance of OP rats.     

Fractional oxidation of chylomicron-derived oleate is greater than that of palmitate in healthy adults fed frequent small meals

Differences in oxidation of individual dietary fatty acids could contribute to the effect of dietary fat composition on risk factors for non-insulin-dependent diabetes mellitus and cardiovascular disease. Using a novel stable isotope technique, we compared fractional oxidation of chylomicron-derived oleate and palmitate in 10 healthy adults in a crossover study. 1-(13)C-labeled oleate or palmitate was emulsified into a eucaloric formula diet administered each 20 min for 7 h to produce a plateau in excretion of (13)C label in breath CO(2). Unlabeled oleate and palmitate each provided 16% of dietary energy, and other fatty acids provided 8% of energy. Total dietary fat was 40% of energy, carbohydrate was 46%, and protein was 14%. Diet without tracer was fed for 2 h before beginning tracer administration to establish a baseline fed state. Relative oxidation of oleate versus palmitate was defined as fractional oxidation of oleate divided by fractional oxidation of palmitate. Relative oxidation averaged 1.21 (99.5% confidence interval = 1.03;-1.39), indicating that fractional oxidation of oleate was significantly greater than that of palmitate.     

AT1-receptor antagonism reverses the blood pressure elevation associated with diet-induced obesity

Previous studies in our laboratory demonstrated that rats exhibiting obesity in response to a moderately high-fat (MHF) diet developed hypertension associated with activation of the local and systemic renin-angiotensin system. In this study, we examined the effect of the angiotensin type 1 (AT(1))-receptor antagonist, losartan, on blood pressure in obesity-prone (OP) and obesity-resistant (OR) rats fed a MHF diet. Using telemetry monitoring, we characterized the evolution of blood pressure elevations during the development of obesity. Male Sprague-Dawley rats were implanted with telemetry transducers for chronic monitoring of blood pressure, and baseline measurements were obtained. Rats were then switched to the MHF diet (32% kcal as fat) and were segregated into OP and OR groups at week 5. At week 9 on the MHF diet, OP rats exhibited significantly greater 24-h mean arterial blood pressure compared with OR rats (OP: 105 +/- 4 mmHg, OR: 96 +/- 2 mmHg; P < 0.05). Elevations in blood pressure in OP rats were manifest as an increase in systolic pressure. Administration of losartan to all rats at week 9 resulted in a reduction in blood pressure; however, losartan had the greatest effect in OP rats (percent decrease in mean arterial pressure by losartan; OP: 19 +/- 4, OR: 10 +/- 2%; P < 0.05). These results demonstrate that elevations in blood pressure occur subsequent to established obesity in rats fed a high-fat diet. Moreover, these results demonstrate the ability of losartan to reverse the blood pressure increase from diet-induced obesity, supporting a primary role for the renin-angiotensin system in obesity-associated hypertension.     

Effects of diet on catabolism and excretion of (26-14C)cholesterol in rats.

The catabolism and excretion of [26-14C]cholesterol was studied in rats on semisynthetic and commercial diets low in fat or containing 15% butter or corn oil. Rats on the low fat commercial diet oxidized the labeled cholesterol to 14CO2 at more than twice the rate of those on the semisynthetic diet. Fecal excretion of labeled lipid was also somewhat higher with the commercial diet. The added fats had little effect on rate of oxidation of cholesterol but dietary corn oil stimulated fecal excretion of labeled lipid. The rate of loss of labeled cholesterol through oxidation and excretion showed a positive correlation with cholesterol biosynthesis, as measured previously by acetate incorporation into cholesterol in rats on the same kinds of diet. A simple method for efficient trapping and counting of 14CO2 was developed, which facilitated measurement of low levels of 14CO2 in expired air. Estimation of bile acid production from the rate of oxidation of [26-14C]cholesterol to expired 14CO2 and the specific activity of plasma cholesterol gave somewhat higher values than those obtained by other methods. Possible reasons for this difference are discussed.     

Caralluma fimbriata and metformin protection of rat pancreas from high fat diet induced oxidative stress

A high fat diet promotes oxidative stress, which contributes to the development of pancreatic fibrosis. We compared the protective effects of a hydroalcoholic extract of Caralluma fimbriata (CFE) to metformin (Met) in the pancreas of Wistar rats fed a high fat diet. The experimental animals were divided into five groups: control (C), treated with CFE (C + CFE), treated with high fat diet (HFD), high fat diet treated with CFE (HFD + CFE), and high fat diet treated with metformin (Met) (HFD + Met). CFE was administered orally to groups C + CFE and HFD + CFE rats for 90 days. Met was given to the HFD + Met group. After 90 days, oxidative stress markers in the pancreas including reduced glutathione (GSH), lipid oxidation (LO), protein oxidation (PO), and activities of antioxidant and polyol pathway enzymes, aldose reductase (AR) and sorbitol dehydrogenase (SDH) were assayed and tissue histology was examined. Establishment of oxidative stress in high fat diet fed rats was verified by elevated LO and PO, decreased GSH, decreased activities of antioxidants and increased activities of polyol pathway enzymes. Oxidative stress was prevented in HFD + CFE and HFD + Met groups. Group C + CFE exhibited improved antioxidant status compared to group C. CFE treatment prevented high fat diet induced acinar cell degeneration, necrosis, edema and hemorrhage. CFE could be used as adjuvant therapy for preventing or managing high fat diet induced pancreatic damage.     

The skeletal muscle Wnt pathway may modulate insulin resistance and muscle development in a diet-induced obese rat model

The Wnt signaling pathway is involved in lipid metabolism and obesity development. Skeletal muscle, a pivotal tissue for metabolism, is regulated by the Wnt signaling. However, little is known of this pathway's involvement in insulin sensitivity and myogenesis in animals. The current study focused on the potential role of Wnt signaling in insulin sensitivity and myogenic events and its further impact on intramuscular fat accumulation. Obesity resistant (OR) and obesity prone (OP) rats were fed a high-fat (HF, 45% kcal fat) diet for 13 weeks. Body weight and circulating triglyceride (TG) were measured and gastrocnemius muscle was collected for analysis of gene expression and protein amount. OP rats had higher body weight and blood TG than OR, and our study demonstrated that the skeletal muscle of OR and OP rats had different levels of β-catenin, which also corresponded to the expression of Wnt downstream genes. The expression of insulin receptor substrate (IRS) was significantly lower in OP than OR skeletal muscle, as was the protein amount of phosphorylated Akt, myocyte enhancer factor-2 (MEF2), and GLUT4. Expression of Myogenic regulatory factor (Myf) 5 and Myf3 (MyoD) were decreased significantly in OP skeletal muscle when compared to OR. Additionally, intramuscular fat was higher in OP than in OR rats. Thus, we propose that the differential Wnt signaling in the skeletal muscle of OR and OP rats is highly likely associated with the differences in insulin sensitivity and myogenic capability in these two strains.     

Photoperiod regulates dietary preferences and energy metabolism in young developing Fischer 344 rats but not in same-age Wistar rats

The effects of photoperiod on dietary preference were examined using young growing Fischer 344 and Wistar rats, which are seasonal and nonseasonal breeders, respectively. Rats were provided a low-fat, high-carbohydrate diet (LFD: 66/10/24% energy as carbohydrate/fat/protein) and high-fat, low-carbohydrate diet (HFD: 21/55/24% energy as carbohydrate/fat/protein) simultaneously under long- (LD: 16 h light/day) and short-day (SD: 8 h light/day) conditions for 3 wk. Fischer 344 rats preferred the LFD to the HFD under the LD condition, whereas preference for both diets was equivalent under the SD condition. Consequently, their body weight and total energy intake exhibited 11-15 and 10-13% increases, respectively, under the LD condition. Calculation of energy intake from macronutrients revealed that rats under the LD condition consumed 20-24 and 9-13% higher energy of carbohydrates and proteins, respectively, than those under the SD condition. In contrast, Wistar rats preferred the LFD to the HFD irrespective of photoperiod and exhibited no photoperiodic changes in any parameters examined. Next, Fischer 344 rats were provided either the LFD or HFD for 3 wk under LD or SD conditions. Calorie intake was 10% higher in the rats fed the LFD than those fed the HFD under SD condition. However, rats under LD condition exhibited 5-10, 14, and 64% increases in body weight, epididymal fat mass, and plasma leptin levels, respectively, compared with those under the SD condition irrespective of dietary composition. In conclusion, photoperiod regulates feeding and energy metabolism in young growing Fischer 344 rats via the interactions with dietary macronutrient composition.     

Fat adaptation followed by carbohydrate loading compromises high-intensity sprint performance.

The aim of this study was to investigate the effect of a high-fat diet (HFD) followed by 1 day of carbohydrate (CHO) loading on substrate utilization, heart rate variability (HRV), effort perception [rating or perceived exertion (RPE)], muscle recruitment [electromyograph (EMG)], and performance during a 100-km cycling time trial. In this randomized single-blind crossover study, eight well-trained cyclists completed two trials, ingesting either a high-CHO diet (HCD) (68% CHO energy) or an isoenergetic HFD (68% fat energy) for 6 days, followed by 1 day of CHO loading (8-10 g CHO/kg). Subjects completed a 100-km time trial on day 1 and a 1-h cycle at 70% of peak oxygen consumption on days 3, 5, and 7, during which resting HRV and resting and exercising respiratory exchange ratio (RER) were measured. On day 8, subjects completed a 100-km performance time trial, during which blood samples were drawn and EMG was recorded. Ingestion of the HFD reduced RER at rest (P < 0.005) and during exercise (P < 0.01) and increased plasma free fatty acid levels (P < 0.01), indicating increased fat utilization. There was a tendency for the low-frequency power component of HRV to be greater for HFD-CHO (P = 0.056), suggestive of increased sympathetic activation. Overall 100-km time-trial performance was not different between diets; however, 1-km sprint power output after HFD-CHO was lower (P < 0.05) compared with HCD-CHO. Despite a reduced power output with HFD-CHO, RPE, heart rate, and EMG were not different between trials. In conclusion, the HFD-CHO dietary strategy increased fat oxidation, but compromised high intensity sprint performance, possibly by increased sympathetic activation or altered contractile function.     

Activation of the systemic and adipose renin-angiotensin system in rats with diet-induced obesity and hypertension

In obesity-related hypertension, activation of the renin-angiotensin system (RAS) has been reported despite marked fluid volume expansion. Adipose tissue expresses components of the RAS and is markedly expanded in obesity. This study evaluated changes in components of the adipose and systemic RAS in diet-induced obese hypertensive rats. RAS was quantified in adipose tissue and compared with primary sources for the circulating RAS. Male Sprague-Dawley rats were fed either a low-fat (LF; 11% kcal as fat) or moderately high-fat (32% kcal as fat) diet for 11 wk. After 8 wk, rats fed the moderately high-fat diet segregated into obesity-prone (OP) and obesity-resistant (OR) groups based on their body weight gain (body weight: OR, 566 +/- 10; OP, 702 +/- 20 g; P < 0.05). Mean arterial blood pressure was increased in OP rats (LF: 97 +/- 2; OR: 97 +/- 2; OP: 105 +/- 1 mmHg; P < 0.05). Quantification of mRNA expression by real-time PCR demonstrated a selective increase (2-fold) in angiotensinogen gene expression in retroperitoneal adipose tissue from OP vs. OR and LF rats. Similarly, plasma angiotensinogen concentration was increased in OP rats (LF: 390 +/- 48; OR: 355 +/- 24; OP: 530 +/- 22 ng/ml; P < 0.05). In contrast, other components of the RAS were not altered in OP rats. Marked increases in the plasma concentrations of angiotensin peptides were observed in OP rats (angiotensin II: LF: 95 +/- 31; OR: 59 +/- 20; OP: 295 +/- 118 pg/ml; P < 0.05). These results demonstrate increased activity of the adipose and systemic RAS in obesity-related hypertension.     

Low‐carbohydrate High‐fat Diets: Regulation of Energy Balance and Body Weight Regain in Rats

The aim of the current investigations was to examine the effects of a low‐carbohydrate high‐fat diet (LC‐HFD) on body weight, body composition, growth hormone (GH), IGF‐I, and body weight regain after stopping the dietary intervention and returning the diet back to standard laboratory chow (CH). In study one, both adolescent and mature male Wistar rats were maintained on either an isocaloric LC‐HFD or CH for 16 days before having their diet switched. In study two, mature rats were maintained on either LC‐HFD or CH for 16 days to determine the effects of the LC‐HFD on fat pad weight. LC‐HFD leads to body weight loss in mature rats (P < 0.01) and lack of body weight gain in adolescent rats (P < 0.01). Despite less body weight, increased body fat was observed in rats maintained on LC‐HFD (P < 0.05). Leptin concentrations were higher (P < 0.05), and IGF‐I (P < 0.01) concentrations were reduced in the LC‐HFD rats. When the diet was returned to CH following LC‐HFD, body weight regain was above and beyond that which was lost (P < 0.01). The LC‐HFD resulted in increased body fat and had a negative effect upon both GH and IGF‐I concentrations, which might have implications for the accretion and maintenance of lean body mass (LBM), normal growth rate and overall metabolic health. Moreover, when the LC‐HFD ceases and a high‐carbohydrate diet follows, more body weight is regained as compared to when the LC‐HFD is consumed, in the absence of increased energy intake.     

Trafficking of dietary oleic, linolenic, and stearic acids in fasted or fed lean rats

Increasing evidence supports the notion that there are significant differences in the health effects of diets enriched in saturated, as opposed to monounsaturated or polyunsaturated fat. However, the current understanding of how these types of fat differ in their handling by relevant tissues is incomplete. To examine the effects of fat type and nutritional status on the metabolic fate of dietary fat, we administered (14)C-labeled oleic, linolenic, or stearic acid with a small liquid meal to male Sprague-Dawley rats previously fasted for 15 h (fasted) or previously fed ad libitum (fed). (14)CO(2) production was measured for 8 h after tracer administration. The (14)C content of gastrointestinal tract, serum, liver, skeletal muscle (soleus, lateral, and medial gastrocnemius), and adipose tissue (omental, retroperitoneal, and epididymal) was measured at six time points (2, 4, 8, 24, and 48 h and 10 days) after tracer administration. Plasma levels of glucose, insulin, and triglyceride were also measured. Oxidation of stearic acid was significantly less than that of either linolenic or oleic acid in both the fed and fasted states. This reduction was in part explained by a greater retention of stearic acid within skeletal muscle and liver. Oxidation of oleate and stearate were significantly lower in the fed state than in the fasted state. In the fasted state, liver and skeletal muscle were quantitatively more important than adipose tissue in the uptake of dietary fat tracers during the immediate postprandial period. In contrast, adipose tissue was quantitatively more important than skeletal muscle or liver in the fed state. The movement of carbons derived from dietary fat between tissues is a complex time-dependent process, which varies in response to the type of fat ingested and the metabolic state of the organism.     

Leptin secretion after a high-fat meal in normal-weight rats: strong predictor of long-term body fat accrual on a high-fat diet

The objective of this study was to investigate meal-related endocrine changes that permit one to identify Sprague-Dawley rats at normal weight that are prone (OP) vs. resistant (OR) to obesity. In blood collected via chronic cardiac catheters, a 2-h high-fat meal (HFM, 50% fat, 40 kcal) at dark onset caused a significant increase in leptin, insulin, and triglycerides compared with premeal levels. Similar to patterns in already obese compared with lean rats on a high-fat diet, these meal-induced endocrine changes in normal-weight rats on lab chow were almost twofold larger in OP rats that, compared with OR rats, subsequently accumulated 100% more fat mass on a chronic high-fat diet. These exaggerated endocrine changes were similarly observed in blood collected using a simpler tail vein puncture procedure. In three separate experiments, the HFM-induced rise in leptin was found to be the strongest, positive correlate (r = +0.58, +0.62 and +0.64) of long-term body fat accrual. The lowest (2-5 ng/ml) vs. highest (6-9 ng/ml) scores for this post-HFM leptin measurement identified distinct OR and OP subgroups, respectively, when they were similar in body weight (340-350 g), premeal leptin (2.6-3.4 ng/ml), and meal size (40 kcal). Subsequent tests in these normal-weight OP rats revealed a distinct characteristic compared with OR rats, namely, exaggerated HFM-induced rise in expression of the orexigenic peptide galanin in the paraventricular nucleus. Thus, with this HFM-induced leptin measurement, OP rats can be identified while still at normal weight and then investigated for mechanisms that contribute to their excessive body fat accrual on a high-fat diet.