Fat Deposition In Rats Research Articles

Role of 1, 25-dihydroxyvitamin D3 in liver lipid metabolism induced by methionine-choline-deficient diet in rats

Objective: To investigate the role of 1, 25-dihydroxyvitamin D3 [1.25(OH) (2)D(3)] in liver lipid metabolism so as to provide the clues for elucidating the mechanism of non-alcoholic fatty liver. Methods: 26 SD rats were randomly divided into control group (methionine-choline-sufficient diet, MCS), model group (methionine-choline-deficiency diet, MCD) and intervention group [MCD+1.25(OH) (2)D(3)]. The intervention, control, and model group was given 3 ng/100 g 1.25(OH) (2)D(3) peanut oil solution per day by gavage according to body mass. After 4 weeks the experiment was ended up, and the blood was collected from the inferior vena cava to detect alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The liver tissue was collected to observe the liver morphological and pathological changes (oil red O and HE staining). The changes in the level of liver total triglyceride (TG) content and liver lipid metabolism-related genes [fatty acid transfer protein (FAT/CD36), acetyl-coenzyme A carboxylase (ACC1)] mRNA and protein were detected. One-way analysis of variance was used to compare the means between groups. Results: Oil red O staining and HE staining showed that lipid droplet-vacuoles were significantly increased in the liver tissue of the model group than that of the intervention group. The liver TG content (2.23 ± 0.98) μmol/g of the intervention group was significantly lower than that of the model group (3.53 ± 1.06) μmol/g (F = 5.930, P = 0.035). The ALT content of the intervention group (35.99±9.54) U/L was significantly lower than that of the model group (57.65 ± 19.42) U/L (F = 13.790, P = 0.034). The AST content of the intervention group (16.9 ± 3.73) U/L was significantly lower than that of the model group (27.81 ± 13.31) U/L (F = 3.084, P = 0.046). The relative expression levels of mRNA and protein (mRNA: 1.21 ± 0.61, protein: 1.54 ± 0.75) of FAT/CD36 in the intervention group were significantly lower than those of the model group (mRNA: 2.31 ± 0.81, protein: 2.83 ± 1.42) (mRNA: F = 8.370, P = 0.001, protein: F = 7.212, P = 0.043). The relative expression level of mRNA and protein of ACC1 (mRNA: 0.89 ± 0.54, protein: 0.28 ± 0.11) were also significantly lower than those in model group (mRNA: 1.39 ± 0.19, protein: 0.47 ± 0.24) (mRNA: F = 3.948, P = 0.036, protein: F = 10.933, P = 0.048). Conclusion: 1.25(OH) (2)D(3) can reduce liver fat deposition in rats fed with MCD by inhibiting the expression of fat / CD36 and ACC1.

Different Ratios of Corn and Coconut Oil Blends in High‐Fat Diets Influence Fat Deposition without Altering Metabolic Biomarkers in Male Rats

AbstractThe effects of high‐fat diets with the recommended dietary linoleic acid (LA) intake levels on health outcomes have not been studied extensively. This study investigated the effects of high‐fat diets containing different weight ratios of coconut and corn oil with LA levels of <1.00% of energy (very low LA), 2.80% of energy (low LA), 5.80% of energy (moderate LA), and 9.70% of energy (high LA) on fat deposition and selected metabolic biomarkers of male Sprague‐Dawley rats. Their initial and terminal body weights are recorded. Blood, adipose tissue, and liver samples are obtained for analysis after an 8‐week feeding intervention. Compared with the very low‐LA diet, the high‐LA diet resulted in higher body weight gain and epididymal fat deposition. No significant differences are observed in liver‐to‐body weight ratio, blood glucose, visfatin, and leptin levels between the test diets. Serum tumor necrosis factor‐alpha (TNF‐α), insulin, and C‐peptide levels do not significantly increase with the increase in dietary LA levels. High‐LA diet results in higher LA levels in the liver and adipose tissue. It is concluded that a high‐fat diet containing high LA levels induced body weight gain and epididymal fat deposition in rats but has no effect on selected metabolic biomarkers.Practical applications: Linoleic acid (LA) (C18:2) plays an important role as one of the nutritional elements to meet the daily essential fatty acid requirements. However, a full understanding is perplexed by the various ways that LA can be included in the diet when there is a recommendation to substitute saturated fatty acid (SFA), trans‐ or n‐3 fatty acids intake. The data provide additional findings on the effects of excessive dietary intake of LA (C18:2) on fat deposition when different levels of SFAs are replaced.

Long-term administration of DHEA prevents fat deposition in rats fed a high-fat diet

The effects of dehydroepiandrosterone (DHEA) on lipid metabolism and lipogenic gene mRNA expression in rats subjected to a high-fat diet were determined. Totally 75 rats were randomly divided into 5 groups: control group 1 fed a normal diet (NCG), and groups 2–5 fed a high-fat diet with 0 (HCG), 25 (HLG), 50 (HMG), 100 (HHG) mg DHEA per kg body weight via gavage once a day for 8 weeks, respectively. DHEA significantly decreased body weight in HMG group as compared with HCG group (P < 0.05). Hepatic triglyceride and total cholesterol contents were decreased in HMG and HHG groups (P < 0.05), and hepatic lipase activity in HMG group was higher (P < 0.01) than in HCG group. Fatty acid synthesis (FAS) mRNA level was decreased in HLG and HHG groups (P < 0.01), and sterol response element binding protein-1 (SREBP-1) mRNA level was decreased in HMG and HHG groups when compared with HCG group (P < 0.01). Acyl-CoA oxidase (ACO) and liver carnitine palmitoyl transferase-1 (LCPT-1) mRNA abundance was decreased in HLG and HHG groups (P < 0.01), whereas hormone sensitive lipase (HSL) mRNA level was increased in HMG group as compared with HCG group (P < 0.05). These results indicated that long-term administration of DHEA reduced the synthesis of endogenous triglycerides by inhibiting SREBP-1 and FAS expression, and augmented the lipolysis of exogenous triglycerides through enhancing HSL expression, which eventually led to reduced fat deposition in rats fed a high-fat diet.

Branched-chain amino acids alleviate nonalcoholic steatohepatitis in rats

Nonalcoholic steatohepatitis (NASH) is a prevalent disease in countries around the world. The branched-chain amino acids (BCAAs) leucine, isoleucine, and valine cannot be synthesized by the body and have been shown to promote muscle buildup; thus, it is logical to suggest that BCAAs can reduce fat deposition in the body. We used gonadectomized rats fed a high-fat diet to investigate the effects of BCAAs on lipid metabolism over an 8-week experimental period. Body composition, tissue histology, plasma lipid indices, and hormone levels were examined. We demonstrated that the body weights of rats were not significantly decreased but the mesenteric fat was significantly decreased (p < 0.05) in BCAA-treated rats. In addition, BCAAs decreased plasma lipid levels and fat deposition in the liver. At week 4, when the untreated rats displayed macrovesicular steatosis, BCAA-treated rats had only macrovesicular droplets in their hepatocytes. At week 8, when the untreated rat livers displayed profound inflammation and cirrhosis, BCAA-treated rat livers remained in the macrovesicular stage of steatosis. BCAAs induced higher blood glucose and plasma insulin levels (p < 0.05). BCAAs also improved liver blood flow by increasing mean arterial blood pressure and decreasing portal pressure, which helped delay the change in blood flow pattern to that of cirrhosis. BCAAs also induced the skeletal muscle to express higher levels of branched-chain α-keto acid dehydrogenase E1α, which indicates an enhanced metabolic capacity of BCAAs in muscle tissue. This study clearly demonstrates the effects of BCAAs on the amelioration of fat deposition in rats fed a high-fat diet.

Fermented Wheat Germ Extract (Avemar) in the Treatment of Cardiac Remodeling and Metabolic Symptoms in Rats

Avemar, a product of industrial fermentation of wheat germ with a standardized content of benzoquinone and plant flavonoids, has been tested as an anti-cancer and immunomodulatory dietary supplement. Proposed mechanisms include anti-oxidant and anti-inflammatory actions. This study has determined whether these actions of Avemar may also be useful in the treatment of cardiovascular diseases. Two experimental rat models of cardiovascular remodeling were used in this project: the deoxycorticosterone acetate (DOCA)-salt-induced model of chronic hypertension (study I) and a high-carbohydrate/high-fat diet-induced model producing chronic symptoms of the metabolic syndrome and its associated cardiovascular complications (study II). Our results in these rat models of hypertension and diet-induced obesity show that treatment with Avemar improved cardiac function, decreased macrophage infiltration resulting in decreased collagen deposition in the ventricular myocardium, reversed an increased stiffness of the left ventricle in the diseased hearts and attenuated increased plasma malondialdehyde concentrations. In addition to the changes in the heart, Avemar reversed glucose intolerance, normalized systolic blood pressure and decreased visceral fat deposition in rats fed a high-fat/high-carbohydrate diet. In conclusion, the fermented wheat germ extract Avemar has a potential role in attenuating chronic hypertension, diabetes or metabolic syndrome-induced cardiovascular symptoms along with metabolic abnormalities such as glucose tolerance and obesity.

18-Methoxycoronaridine: a potential new treatment for obesity in rats?

Excessive eating often leads to obesity. Although a variety of neurotransmitters and brain regions are involved in modulating food intake, a role of accumbal dopamine is thought to be critical for several aspects of this behavior. Since 18-methoxycoronaridine (18-MC), a selective antagonist of alpha3beta4 nicotinic receptors, was previously shown to alter dopamine release in the nucleus accumbens in response to chronic injections of cocaine and morphine, this drug could be a promising therapy for abnormal eating behavior. Assess the effect of 18-MC on the consumption of sucrose (15%) vs. water in a self-administration paradigm and on the intake of freely available palatable fluids (i.e., 5% sucrose, 0.1% saccharin, and 0.6% saline solutions) as well as on water intake. Determine whether repeated administration of 18-MC (20 mg/kg i.p.) affects weight gain, food intake, and fat deposition in rats drinking 30% sucrose solution. Acute administration of 18-MC (10-40 mg/kg i.p.) reduced operant responding for sucrose and decreased ad libitum ingestion of sucrose, saccharin, and saline. The highest dose of 18-MC also reduced consumption of water when palatable fluids were not available. In rats having unlimited access to sucrose (30%), chronic treatment with 18-MC (20 mg/kg i.p.) prevented sucrose-induced increases in body weight, decreased fat deposition, and reduced consumption of sucrose while not altering food intake. These data suggest that antagonism of alpha3beta4 nicotinic receptors may be involved in the regulation of intake of palatable substances regardless of its caloric value and may participate in maintaining obesity.

Celecoxib decreases fatty acid synthase expression via down-regulation of c-Jun N-terminal kinase-1.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are inhibitors of cyclooxygenase (COX). Our previous observations that celecoxib, a COX-2-specific inhibitor, not only inhibits rat mammary carcinogenesis, but also decreases fat deposition in rats fed a high-fat diet, prompted us to determine whether celecoxib affects lipid metabolism. At 57 days of age, two groups of 10 female Sprague Dawley rats were pair-fed a high-fat diet with or without 1500 ppm celecoxib for 15 weeks. Compared with controls, celecoxib-treated rats had 44.4% less hepatic triglycerides and 22.6% less intra-abdominal adipose tissue mass. In the liver and adipose tissue of several genes involved in fat metabolism and mobilization that we measured, only fatty acid synthase (FAS) was significantly down-regulated by celecoxib treatment. There were no differences in the level of prostaglandin E(2) in these tissues, indicating that celecoxib decreases fat accumulation by down-regulating FAS through a COX-2-independent mechanism. Among the potential molecular targets by which celecoxib may regulate FAS expression, only c-Jun N-terminal kinase-1 (JNK1) was significantly down-regulated. Furthermore, a known inhibitor of JNK suppressed FAS expression in rat hepatocytes. Our observations suggest that celecoxib suppresses FAS expression and decreases fat accumulation by down-regulating JNK1.

Campest-5-en-3-one, an oxidized derivative of campesterol, activates PPARα, promotes energy consumption and reduces visceral fat deposition in rats

Dietary campest-5-en-3-one (campestenone), an oxidized derivative of campesterol, significantly reduced visceral fat weight and the concentration of triacylglycerol in serum and liver of rats. Dietary campestenone dramatically increased the activities and the mRNA expressions of mitochondrial and peroxisomal enzymes involved in β-oxidation in the liver. Campestenone activated human peroxisome proliferator-activated receptor (PPAR) α as determined using the novel GAL4 ligand-binding domain chimera assay system with coactivator coexpression. In contrast, dietary campestenone reduced the activities and the mRNA expressions of enzymes involved in fatty acid synthesis, except for the malic enzyme. Dietary campestenone decreased the sterol regulatory element binding protein-1 (SREBP-1) mRNA level. Energy expenditure was significantly higher in the feeding of campestenone in rats. Dietary campestenone reduced hepatic cholesterol concentration and increased fecal excretion of neutral steroids originated from cholesterol. Lymphatic absorption of cholesterol was reduced by the coadministration of campestenone in rats cannulated in the thoracic duct. These observations suggest a possibility that campestenone has an ability to prevent coronary heart disease by improving obesity and abnormality of lipid metabolism.

High Glycemic Index Starch Promotes Hypersecretion of Insulin and Higher Body Fat in Rats without Affecting Insulin Sensitivity

In rats, prolonged feeding of high glycemic index (GI) starch results in basal hyperinsulinemia and an elevated insulin response to an intravenous glucose tolerance test (IVGTT). The aim of this study was to assess hepatic and peripheral insulin resistance (IR) using euglycemic hyperinsulinemic clamps. Insulin sensitivity, epididymal fat deposition and fasting leptin concentrations were compared in rats fed isocalorically a low or high GI diet for 7 wk (45% carbohydrate, 35% fat and 20% protein as energy) or a high fat diet (20% carbohydrate, 59% fat and 21% protein as energy) for 4 wk so that final body weights were similar. At the end of the study, high GI rats had higher basal leptin concentration and epididymal fat mass than the low GI group, despite comparable body weights. High GI and high fat feeding both resulted in the higher insulin response during IVGTT, but impaired glucose tolerance was seen only in rats fed high fat. The GI of the diet did not affect basal and clamp glucose uptake or hepatic glucose output, but high fat feeding induced both peripheral and hepatic IR. The findings suggest that hypersecretion of insulin without IR may be one mechanism for increased fat deposition in rats fed high GI diets.

Carnitine supplementation accelerates normalization of food intake depressed during TPN

When total parenteral nutrition (TPN; containing glucose, fat, and amino acids; caloric ratio 50:30:20) providing 100% of the rat's daily caloric intake is given for 3–4 days, food intake rapidly decreases by approximately 85%. After stopping TPN, there is a lag period of 3–4 days before food intake returns to previous level, which appears to be related to fatty acid oxidation and fat deposition. Carnitine plays a key role in the oxidation of fatty acids, and was demonstrated to reduce fat deposition in rats receiving TPN, by increasing beta oxidation. We therefore investigated whether rats receiving TPN supplemented with carnitine may prevent either the decrease or speed up the resumption or normalization of food intake, after TPN is stopped. Fourteen adult Fischer-344 rats had a central venous catheter inserted. After 10 recovery days, controls ( n = 7) were infused with TPN providing 100% of rat's daily caloric intake for 3 consecutive days, followed by 4 more days of normal saline. The carnitine group ( n = 7) received the same solution, but which provided 100 mg/kg/day carnitine. Daily food intake was measured and data were analyzed using ANOVA and Student's t-test. Both parenteral solutions depressed food intake maximally by almost 90% by day 3. Carnitine accelerated the normalization of food intake by decreasing the lag period by 1 day. We conclude that the addition of carnitine enhanced the normalization of post-TPN food intake and argue that this may be on the basis of enhanced fatty acid oxidation, a substrate known to play a significant role in the anorexia induced by TPN.

Resistance to adipocyte hyperplasia in ground squirrels given high-fat diets.

Mammalian hibernators prepare for the winter by depositing fat in existing fat cells. There is little, if any, production of new fat cells. This is curious because equivalent fat deposition in rats is associated with substantial fat cell production. To determine whether degree of weight gain, diet composition, or some special mechanism militating against adipocyte hyperplasia may underlie the absence of adipocyte hyperplasia in hibernators, male Richardson's ground squirrels, Spermophilus richardsonii, were fed a fattening high-fat diet for either 5 mo or 1 yr. The 5-mo high-fat feeding period caused peak body weights to increase 36% relative to the peak body weights seen in control animals fed ordinary chow. Despite this increase, there was no apparent increment in fat cell number in any of the major fat depots. Animals fed the diet for 1 yr reached body weights similar to those of the 5-mo group but showed significant adipocyte hyperplasia in all fat depots studied. Thus adult ground squirrels are clearly capable of enlarging their pool of mature fat cells, but they fail to do so, at least at certain times, in response to conditions of weight gain that cause considerable adipocyte hyperplasia in rats.

Energy Intake, Weight Gain and Fat Deposition in Rats Fed Flavored, Nutritionally Controlled Diets in a Multichoice (“Cafeteria”) Design

The effect of flavor variety on diet selection, energy intake, weight gain and fat deposition was studied in male rats fed flavored, nutritionally controlled, purified diets in a multichoice “cafeteria” (CAF) arrangement. Serum insulin, L-3,3′,5-triiodothyronine (T3) and thyroxine (T4) levels were also determined. Rats fed nutritionally balanced diets containing a variety of preferred flavors and textural forms ad libitum in a CAF design did not consume more energy nor did they gain more weight than rats fed a single choice of nutritionally balanced diet with no modifications in flavor or texture. Feeding high fat, high sucrose diets containing a variety of flavors in a CAF arrangement resulted in higher energy intake, body weight gain, lipid content in fat pads and serum T3 levels than did feeding the nutritionally balanced diet. However, the high fat diet with no added flavors also resulted in an energy intake, body weight gain and lipid content of fat pads at a level equal or close to that produced by the CAF feeding of the flavored, high fat, high sucrose diet. It is therefore concluded that the effect of a variety of food flavors on hyperphagia and fat deposition is of minor importance in purified diets compared to the stimulating effect of the fat in the diet.

The energetic efficiency of growth

Metabolizable energy consumed by a growing animal is partitioned between heat production and gains in body tissues, principally protein and fat. The laws of growth that govern this partition are discussed. The apparent energy costs of protein and fat deposition in rats and pigs are about 53 kJ/g. Heat production is, however, related much more closely to total protein synthesis, most of which takes place in tissues other than ‘meat’. Ways and means of manipulating protein synthesis and the energy cost of growth by nutrition, anabolic agents and anti-microbial growth promoters are considered.

The energetic efficiency of growth

Abstract Metabolizable energy consumed by a growing animal is partitioned between heat production and gains in body tissues, principally protein and fat. The laws of growth that govern this partition are discussed. The apparent energy costs of protein and fat deposition in rats and pigs are about 53 kJ/g. Heat production is, however, related much more closely to total protein synthesis, most of which takes place in tissues other than ‘meat’. Ways and means of manipulating protein synthesis and the energy cost of growth by nutrition, anabolic agents and anti-microbial growth promoters are considered.

Influence of Diet Composition on Nitrogen Balance and Body Composition in Meal-Eating and Nibbling Rats

A series of experiments was conducted to evaluate the influence of meal frequency on nitrogen balance and body composition of rats. Rats were either fed 2 hours per 24 or 48 hours (meal-eaters), or pair-fed to meal-eaters with an automated feeding machine (nibblers). Rats weighing approximately 250 g initially, were fed 10%, 20%, or 30% casein, high-carbohydrate diets or a 20% casein high-fat diet for 7 to 8 weeks. Meal-eaters gained essentially the same amount of body weight as the nibblers. Meal-feeding once per 24 or 48 hours did not adversely influence nitrogen balance or the body composition of the rats. In one experiment, smaller rats, weighing approximately 150 g initially, were utilized. Meal-eaters again, retained as much nitrogen as nibblers, and contained less body fat than the nibblers. In these studies, meal-eating did not cause a depression in nitrogen retention or an increase in body fat deposition in rats.

Comparative growth and fat deposition in rats as influenced by ration fed dam during lactation and that fed rats after weaning

Comparative growth and fat deposition in rats as influenced by ration fed dam during lactation and that fed rats after weaning

Effect of Ambient Temperature and Dietary Amino Acids on Carcass Fat Deposition in Rats

Sixty-three rats of the Sprague-Dawley strain were used in each of two experiments to study the effects of ambient temperature (7, 23 and 33°) on diet utilization. In experiment 1, dietary protein levels and protein-amino acid sources were: A) 31.7%, casein; B) 15.85%, casein; and C) 31.7%, diet B plus casein-simulating crystalline amino acid mixture. The rats, average initial weight of 122 g, were confined to individual metabolism cages and fed ad libitum for 20 days, then killed for carcass analysis. Diet intake increased significantly with decrease in temperature. Gain was highest at 23°, lowest at 7°. Gain-to-feed ratio results were similar at 23 and 33°, with both significantly higher than at 7°. Carcass fat decreased significantly as temperature decreased. For experiment 2, diet C of experiment 1 served as the control and the effects of deletions of certain of the crystalline amino acids were studied. With isonitrogenous diets, omission of the crystalline essential amino acids or of only the basic amino acids increased fat deposition. Carcass fat deposition, however, responded more to ambient temperature than to amino acid imbalance.

Growth Response and Liver Fat Deposition in Rats Fed Bread Mixtures with Varying Levels of Non-Fat Milk Solids and Lysine

Growth Response and Liver Fat Deposition in Rats Fed Bread Mixtures with Varying Levels of Non-Fat Milk Solids and Lysine