Hepatic steatosis and increased adiposity in mice consuming rapidly vs. slowly absorbed carbohydrate

Objective: Non‐alcoholic fatty liver disease (NAFLD) is fast becoming a major public health concern, coincident with the increasing prevalence of obesity. Although lifestyle greatly influences development of NAFLD, the specific dietary causes remain largely unknown. The purpose of this study was to determine whether a diet high in rapidly absorbed carbohydrate (RAC) vs. slowly absorbed carbohydrate (SAC), controlled for confounding dietary factors, causes NAFLD in mice with similar body weight. An animal model was chosen because of logistical and ethical challenges to conducting this study in humans. Research Methods and Procedures: Male 129SvPas mice were fed diets high in either RAC (amylopectin; high glycemic index) or SAC (amylose; low glycemic index) for 25 weeks. Diets were controlled for macronutrient and micronutrient content, differing only in starch type. Body weight and composition were measured throughout the study. Hepatic and plasma triacylglycerol concentrations were quantified at the end of the study. Results: Body weight was not significantly different between the two groups. However, total body adiposity increased twice as much, in absolute terms, in the mice fed RAC vs. SAC (12.2 ± 2.9% vs. 6.1 ± 4.2%, p < 0.0001). Hepatic triacylglycerol content was 2‐fold greater in the RAC group (20.7 ± 9.4 vs. 9.6 ± 4.9 mg/g, p = 0.01). In addition, plasma insulin and triacylglycerol concentrations were higher in the RAC group. Discussion: A diet high in RAC causes accumulation of fat in liver, adipose tissue, and plasma in mice. Therefore, a low glycemic index diet may help prevent or treat NAFLD in humans.     

Glycomacropeptide, a low-phenylalanine protein isolated from cheese whey, supports growth and attenuates metabolic stress in the murine model of phenylketonuria

Phenylketonuria (PKU) is caused by a mutation in the phenylalanine (phe) hydroxylase gene and requires a low-phe diet plus amino acid (AA) formula to prevent cognitive impairment. Glycomacropeptide (GMP) contains minimal phe and provides a palatable alternative to AA formula. Our objective was to compare growth, body composition, and energy balance in Pah(enu2) (PKU) and wild-type mice fed low-phe GMP, low-phe AA, or high-phe casein diets from 3-23 wk of age. The 2 × 2 × 3 design included main effects of genotype, sex, and diet. Fat and lean mass were assessed by dual-energy X-ray absorptiometry, and acute energy balance was assessed by indirect calorimetry. PKU mice showed growth and lean mass similar to wild-type littermates fed the GMP or AA diets; however, they exhibited a 3-15% increase in energy expenditure, as reflected in oxygen consumption, and a 3-30% increase in food intake. The GMP diet significantly reduced energy expenditure, food intake, and plasma phe concentration in PKU mice compared with the casein diet. The high-phe casein diet or the low-phe AA diet induced metabolic stress in PKU mice, as reflected in increased energy expenditure and intake of food and water, increased renal and spleen mass, and elevated plasma cytokine concentrations consistent with systemic inflammation. The low-phe GMP diet significantly attenuated these adverse effects. Moreover, total fat mass, %body fat, and the respiratory exchange ratio (CO(2) produced/O(2) consumed) were significantly lower in PKU mice fed GMP compared with AA diets. In summary, GMP provides a physiological source of low-phe dietary protein that promotes growth and attenuates the metabolic stress induced by a high-phe casein or low-phe AA diet in PKU mice.     

High-glycemic index carbohydrates abrogate the antiobesity effect of fish oil in mice

Fish oil rich in n-3 polyunsaturated fatty acids is known to attenuate diet-induced obesity and adipose tissue inflammation in rodents. Here we aimed to investigate whether different carbohydrate sources modulated the antiobesity effects of fish oil. By feeding C57BL/6J mice isocaloric high-fat diets enriched with fish oil for 6 wk, we show that increasing amounts of sucrose in the diets dose-dependently increased energy efficiency and white adipose tissue (WAT) mass. Mice receiving fructose had about 50% less WAT mass than mice fed a high fish oil diet supplemented with either glucose or sucrose, indicating that the glucose moiety of sucrose was responsible for the obesity-promoting effect of sucrose. To investigate whether the obesogenic effect of sucrose and glucose was related to stimulation of insulin secretion, we combined fish oil with high and low glycemic index (GI) starches. Mice receiving the fish oil diet containing the low-GI starch had significantly less WAT than mice fed high-GI starch. Moreover, inhibition of insulin secretion by administration of nifedipine significantly reduced WAT mass in mice fed a high-fish oil diet in combination with sucrose. Our data show that the macronutrient composition of the diet modulates the effects of fish oil. Fish oil combined with sucrose, glucose, or high-GI starch promotes obesity, and the reported anti-inflammatory actions of fish oil are abrogated. In conclusion, our data indicate that glycemic control of insulin secretion modulates metabolic effects of fish oil by demonstrating that high-GI carbohydrates attenuate the antiobesity effects of fish oil.     

Modeling Energy Dynamics in Mice with Skeletal Muscle Hypertrophy Fed High Calorie Diets

Retrospective and prospective studies show that lean mass or strength is positively associated with metabolic health. Mice deficient in myostatin, a growth factor that negatively regulates skeletal muscle mass, have increased muscle and body weights and are resistant to diet-induced obesity. Their leanness is often attributed to higher energy expenditure in the face of normal food intake. However, even obese animals have an increase in energy expenditure compared to normal weight animals suggesting this is an incomplete explanation. We have previously developed a computational model to estimate energy output, fat oxidation and respiratory quotient from food intake and body composition measurements to more accurately account for changes in body composition in rodents over time. Here we use this approach to understand the dynamic changes in energy output, intake, fat oxidation and respiratory quotient in muscular mice carrying a dominant negative activin receptor IIB expressed specifically in muscle. We found that muscular mice had higher food intake and higher energy output when fed either chow or a high-fat diet for 15 weeks compared to WT mice. Transgenic mice also matched their rate of fat oxidation to the rate of fat consumed better than WT mice. Surprisingly, when given a choice between high-fat diet and Ensure® drink, transgenic mice consumed relatively more calories from Ensure® than from the high-fat diet despite similar caloric intake to WT mice. When switching back and forth between diets, transgenic mice adjusted their intake more rapidly than WT to restore normal caloric intake. Our results show that mice with myostatin inhibition in muscle are better at adjusting energy intake and output on diets of different macronutrient composition than WT mice to maintain energy balance and resist weight gain.     

Influence of diet on the storage, mobilization and utilization of energy reserves in trained and untrained rats

The effect of the major dietary energy source (fat or carbohydrate) on some of the adaptations to physical training, particularly body composition and tissue glycogen concentrations, were studied in growing male Wistar rats. Resting liver glycogen concentrations were lower in both trained and sedentary rats fed a high fat diet compared to corresponding rats fed a high carbohydrate (low fat) diet. Trained rats on both diets had higher liver glycogen levels than corresponding sedentary controls. Resting gastrocnemius muscle glycogen concentrations were not influenced by diet or training. Rates of liver and muscle glycogen depletion during a 60-min swim were lower in trained rats but were not influenced by diet. Significant interactions were noted between the dietary energy source and exercise training with respect to body weight gain, body fat content, liver weight and liver glycogen concentrations.     

Inactivation of PKCtheta leads to increased susceptibility to obesity and dietary insulin resistance in mice

In this study, we investigated the metabolic phenotype of PKCtheta knockout mice (C57BL/6J) on chow diet and high-fat diet (HFD). The knockout (KO) mice are normal in growth and reproduction. On the chow diet, body weight and food intake were not changed in the KO mice; however, body fat content was increased with a corresponding decrease in body lean mass. Energy expenditure and spontaneous physical activity were decreased in the KO mice. On HFD, energy expenditure and physical activity remained low in the KO mice. The body weight and fat content were increased rapidly in the KO mice. At 8 wk on HFD, severe insulin resistance was detected in the KO mice with hyperinsulinemic euglycemic clamp and insulin tolerance test. Insulin action in both hepatic and peripheral tissues was reduced in the KO mice. Plamsa free fatty acid was increased, and expression of adiponectin in the adipose tissue was decreased, in the KO mice on HFD. This study suggests that loss of PKCtheta reduces energy expenditure and increases the risk of dietary obesity and insulin resistance in mice.     

Self‐Selected Macronutrient Diet Affects Energy and Glucose Metabolism in Brown Fat‐Ablated Mice

Objective: Obese transgenic UCP‐DTA mice have largely ablated brown adipose tissue and develop obesity and diabetes, which are highly susceptible to a high‐fat diet. We investigated macronutrient self‐selection and its effect on development of obesity, diabetes, and energy homeostasis in UCP‐DTA mice. Research Methods and Procedures: UCP‐DTA and wild‐type littermates were fed a semisynthetic macronutrient choice diet (CD) ad libitum from weaning until 17 weeks. Energy homeostasis was assessed by measurement of food intake, food digestibility, body composition, and energy expenditure. Diabetes was assessed by blood glucose measurements and insulin tolerance test. Results: Wild‐type and UCP‐DTA mice showed a high fat preference and increased energy digestion on CD compared with a low‐fat standard diet. On CD, wild‐type mice accumulated less body fat (16.9%) than UCP‐DTA (32.6%) mice, although they had a higher overall energy intake. Compared with wild‐type mice, resting metabolic rate was reduced in UCP‐DTA mice irrespective of diet. UCP‐DTA mice progressively decreased their carbohydrate intake, resulting in an almost complete avoidance of carbohydrate. UCP‐DTA mice developed severe insulin resistance but showed decreased fed and fasted blood glucose on CD. Discussion: In contrast to wild‐type mice, UCP‐DTA mice were not able to reduce their weight gain efficiency on CD. This suggests that, because of the high fat preference of the background strain and the increased metabolic efficiency, brown adipose tissue‐deficient mice still develop obesity and insulin resistance on a macronutrient CD even when decreasing overall energy intake. Through the avoidance of carbohydrates, however, they are able to maintain normoglycemia.     

Energy intake, diet composition, energy expenditure, and body fatness of adolescents in northern Greece

Objective: The purpose of this study was to examine energy intake, energy expenditure, diet composition, and obesity of adolescents in Northern Greece. Research Methods and Procedures: Anthropometric measurements were taken for all participants. Height, weight, and skinfold thickness at two sites were measured. BMI and percentage body fat were calculated. Energy intake and macronutrient and micronutrient intakes were determined by a 3‐day weighed dietary diary. Energy expenditure was calculated based on calculated resting metabolic rate (RMR) 1 multiplied by an activity factor based on reported physical activity. Results: Thirty‐one percent of boys and 21% of girls had BMI corresponding to ≥25 kg/m² at 18 years and were classified as overweight. Both overweight boys and girls reported a lower energy intake compared with their non‐overweight counterparts when expressed as kilocalories per kilogram body weight. Overweight children had a higher negative energy balance. Both overweight and non‐overweight adolescents had higher than recommended fat intakes. Mean daily carbohydrate, protein, and fat intake, expressed as grams per kilogram body weight, of overweight adolescents were significantly lower compared with the non‐overweight adolescents. Total daily carbohydrate intake, when expressed in grams, was found to be higher for non‐overweight adolescents. Both overweight boys and girls had lower iron intakes than their non‐overweight counterparts. Overweight boys had statistically lower fiber and niacin intakes than non‐overweight boys. Both overweight and non‐overweight adolescents had lower than recommended iron intakes. Furthermore, overweight adolescents consumed more snacks (potato chips, chocolate bars, pizza, cheese pie, and cream pie), more sugar, jam, and honey, and fewer legumes, vegetables, and fruits than their non‐overweight counterparts. Discussion: Reported energy intake of overweight adolescents was lower than their non‐overweight counterparts. Regarding diet composition overweight subjects had significantly lower intakes of carbohydrates compared with non‐overweight subjects. The food consumption pattern of overweight children showed less adherence to the traditional Mediterranean diet.     

Diet‐Induced Changes in Stearoyl‐CoA Desaturase 1 Expression in Obesity‐Prone and ‐Resistant Mice

Objective: To investigate stearoyl‐coenzyme A desaturase (SCD) 1 expression in obesity‐prone C57BL/6 mice and in obesity‐resistant FVB mice to explore the relationship of SCD1 expression and susceptibility to diet‐induced obesity. Research Methods and Procedures: Nine‐week‐old C57BL/6 and FVB mice were fed either a high‐ or low‐fat diet for 8 weeks. Body weight and body composition were measured before and at weeks 4 and 8 of the study. Energy expenditure was measured at weeks 1 and 5 of the study. Hepatic SCD1 mRNA was measured at 72 hours and at the end of study. Plasma leptin and insulin concentrations were measured at the end of study. Results: When C57BL/6 mice were switched to a calorie‐dense high‐fat diet, animals gained significantly more body weight than those maintained on a low‐calorie density diet primarily due to increased fat mass accretion. Fat mass continued to accrue throughout 8 weeks of study. Increased calorie intake did not account for all weight gain. On the high‐fat diet, C57BL/6 mice decreased their energy expenditure when compared with mice fed a low‐fat diet. In response to 8 weeks of a high‐fat diet, SCD1 gene expression in liver increased >2‐fold. In contrast, feeding a high‐fat diet did not change body weight, energy expenditure, or SCD1 expression in FVB mice. Discussion: Our study showed that a high‐fat hypercaloric diet increased body adiposity first by producing hyperphagia and then by decreasing energy expenditure of mice susceptible to diet‐induced obesity. Consumption of a high‐fat diet in species predisposed to obesity selectively increased SCD1 gene expression in liver.     

Deleterious effects of sugar and protective effects of starch on cardiac remodeling, contractile dysfunction, and mortality in response to pressure overload

Little is known about the effects of the composition of dietary carbohydrate on the development of left ventricular (LV) hypertrophy (LVH) and heart failure (HF) under conditions of pressure overload. The objective of this study was to determine the effect of carbohydrate composition on LVH, LV function, and mortality in a mouse model of chronic pressure overload. Male C57BL/6J mice of 6 wk of age (n = 14-16 mice/group) underwent transverse aortic constriction (TAC) or sham surgery and were fed either standard chow (STD; 32% corn starch, 35% sucrose, 3% maltodextrin, and 10% fat expressed as a percent of the total energy), high-starch chow (58% corn starch, 12% maltodextrin, and 10% fat), or high-fructose chow (9% corn starch, 61% fructose, and 10% fat). After 16 wk of treatment, mice with TAC fed the STD or high-fructose diets exhibited increased LV mass, larger end-diastolic and end-systolic diameters, and decreased ejection fraction compared with sham. The high-starch diet, in contrast, prevented changes in LV dimensions and contractile function. Cardiac mRNA for myosin heavy chain-beta was increased dramatically in the fructose-fed banded animals, as was mortality (54% compared with 8% and 29% in the starch and STD banded groups, respectively). In conclusion, a diet high in simple sugar was deleterious, resulting in the highest mortality and expression of molecular markers of cardiac dysfunction in TAC animals compared with sham, whereas a high-starch diet blunted mortality, increases in cardiac mass, and contractile dysfunction.     

Postnatal deficiency of essential fatty acids in mice results in resistance to diet-induced obesity and low plasma insulin during adulthood

Our objective was to investigate the long-term metabolic effects of postnatal essential fatty acid deficiency (EFAD). Mouse dams were fed an EFAD diet or an isoenergetic control diet 4 days before delivery and throughout lactation. The pups were weaned to standard diet (STD) and were later subdivided into two groups: receiving high fat diet (HFD) or STD. Body composition, energy expenditure, food intake and leptin levels were analyzed in adult offspring. Blood glucose and plasma insulin concentrations were measured before and during a glucose tolerance test. EFAD offspring fed STD were leaner with lower plasma leptin and insulin concentrations compared to controls. EFAD offspring fed HFD were resistant to diet-induced obesity, had higher energy expenditure and lower levels of plasma leptin and insulin compared to controls. These results indicate that the fatty acid composition during lactation is important for body composition and glucose tolerance in the adult offspring.     

Effect of Diets Containing Sucrose vs. D‐tagatose in Hypercholesterolemic Mice

Effects of functional sweeteners on the development of the metabolic syndrome and atherosclerosis are unknown. The objective was to compare the effect of dietary carbohydrate in the form of sucrose (SUCR) to D‐tagatose (TAG; an isomer of fructose currently used as a low‐calorie sweetener) on body weight, blood cholesterol concentrations, hyperglycemia, and atherosclerosis in low‐density lipoprotein receptor deficient (LDLr^−/−) mice. LDLr^−/− male and female mice were fed either standard murine diet or a diet enriched with TAG or SUCR as carbohydrate sources for 16 weeks. TAG and SUCR diets contained equivalent amounts (g/kg) of protein, fat, and carbohydrate. We measured food intake, body weight, adipocyte diameter, serum cholesterol and lipoprotein concentrations, and aortic atherosclerosis. Macrophage immunostaining and collagen content were examined in aortic root lesions. CONTROL and TAG‐fed mice exhibited similar energy intake, body weights and blood glucose and insulin concentrations, but SUCR‐fed mice exhibited increased energy intake and became obese and hyperglycemic. Adipocyte diameter increased in female SUCR‐fed mice compared to TAG and CONTROL. Male and female SUCR‐fed mice had increased serum cholesterol and triglyceride concentrations compared to TAG and CONTROL. Atherosclerosis was increased in SUCR‐fed mice of both genders compared to TAG and CONTROL. Lesions from SUCR‐fed mice exhibited pronounced macrophage immunostaining and reductions in collagen content compared to TAG and CONTROL mice. These results demonstrate that in comparison to sucrose, equivalent substitution of TAG as dietary carbohydrate does not result in the same extent of obesity, hyperglycemia, hyperlipidemia, and atherosclerosis.     

Dietary-induced hypertrophic--hyperplastic obesity in mice

Metabolically intact NMRI mice and genetically obese NZO mice were fed ad lib. either a high-carbohydrate diet (standard) or a high-fat diet for a period of about 11 (NMRI mice) or 38 (NZO mice) wk. In both strains of mice, body weight increased more in the groups fed the high-fat diet. However, caloric intake by NMRI mice fed the high-fat diet was less than that of the controls. In NMRI mice fed the high-fat diet, epididymal and subcutaneous fat cell volumes increased; when these mice were fed the standard diet, only epididymal fat cell volume increased. Epididymal and subcutaneous fat cell numbers increased only in the group fed the high-fat diet. In NMRI mice fed either diet, the postprandial blood glucose was lower in older animals, but plasma insulin remained unchanged. The glucose tolerance deteriorated insignificantly. In NZO mice fed either diet, epididymal fat cell volumes and fat cell numbers increased. In this strain of mice the postprandial blood glucose and plasma insulin exhibited the strain-specific pattern, independent of the diet. In older animals fed either diet the glucose tolerance decreased.     

Development and Verification of a Mouse Model for Roux-en-Y Gastric Bypass Surgery with a Small Gastric Pouch

Existing mouse models of Roux-en-Y gastric bypass (RYGB) surgery are not comparable to human RYGB in gastric pouch volume for a large or absent gastric volume. The aim of this study was to develop and characterize a mouse RYGB model that closely replicates gastric pouch size of human RYGB surgery of about 5% of total gastric volume. We established this model in diet-induced obese (DIO) mice of C57BL/6J. This surgery resulted in a sustained 30% weight loss, entirely accounted for by decreased fat mass but not lean mass, compared to sham-operated mice on the high fat diet. Compared to sham-operated mice, energy expenditure corrected for total body weight was significantly increased by about 25%, and substrate utilization was shifted toward higher carbohydrate utilization at 8 weeks after RYGB when body weight had stabilized at the lower level. The energy expenditure persisted and carbohydrate utilization was even more pronounced when the mice were fed chow diet. Although significantly increased during daytime, overall locomotor activity was not significantly different. In response to cold exposure, RYGB mice exhibited an improved capacity to maintain the body temperature. In insulin tolerance test, exogenous insulin-induced suppression of plasma glucose levels was significantly greater in RYGB mice at 4 weeks after surgery. Paradoxically, food intake measured at 5 weeks after surgery was significantly increased, possibly in compensation for increased fecal energy loss and energy expenditure. In conclusion, this new model is a viable alternative to existing murine RYGB models and the model matches human RYGB surgery in anatomy. This model will be useful for studying molecular mechanisms involved in the beneficial effects of RYGB on body weight and glucose homeostasis.     

Protein-leverage in mice: the geometry of macronutrient balancing and consequences for fat deposition

Objective: The Protein‐Leverage Hypothesis proposes that humans regulate their intake of macronutrients and that protein intake is prioritized over fat and carbohydrate intake, causing excess energy ingestion when diets contain low %protein. Here we test in a model animal, the mouse: (i) the extent to which intakes of protein and carbohydrate are regulated; (ii) if protein intake has priority over carbohydrates so that unbalanced foods low in %protein leads to increased energy intake; and (iii) how such variations in energy intake are converted into growth and storage. Methods and Procedures: We fed mice one of five isocaloric foods having different protein to carbohydrate composition, or a combination of two of these foods (N = 15). Nutrient intake and corresponding growth in lean body mass and lipid mass were measured. Data were analyzed using a geometric approach for analyzing intake of multiple nutrients. Results: (i) Mice fed different combinations of complementary foods regulated their intake of protein and carbohydrate toward a relatively well‐defined intake target. (ii) When mice were offered diets with fixed protein to carbohydrate ratio, they regulated the intake of protein more strongly than carbohydrate. This protein‐leverage resulted in higher energy consumption when diets had lower %protein and led to increased lipid storage in mice fed the diet containing the lowest %protein. Discussion: Although the protein‐leverage in mice was less than what has been proposed for humans, energy intakes were clearly higher on diets containing low %protein. This result indicates that tight protein regulation can be responsible for excess energy ingestion and higher fat deposition when the diet contains low %protein.     

Conjugated Linoleic Acid (CLA), Body Fat,and Apoptosis*

Objective: The objective of the study was to determine if consumption of conjugated linoleic acid (CLA) by mice could induce apoptosis in adipose tissue. Other objectives were to determine the influence of feeding mice CLA for ≤2 weeks on body fat, energy expenditure, and feed intake. Research Methods and Procedures: A mixture of CLA isomers (predominantly c9,t11 and t10,c12) was included in the AIN‐93G diet at 0, 1, and 2%, and fed to mice for 12 days (Trial 1), or was included at 2% and fed to mice for 0, 5, and 14 days (Trial 2). Feed intake was measured daily and energy expenditure was determined by direct calorimetry on day 9 in Trial 1. Retroperitoneal fat pads were analyzed for apoptosis by determination of DNA fragmentation. Results: Dietary CLA reduced feed intake by 10% to 12% (p < 0.01), but either did not influence or did not increase energy expenditure as indicated by heat loss. Body weight was not influenced by consumption of CLA in Trial 1 but was increased (p < 0.01) by CLA in Trial 2. Weights of retroperitoneal, epididymal, and brown adipose tissues were lower (p < 0.01) in animals fed CLA, although liver weight was increased (p < 0.10; Trial 1) or not changed (Trial 2). Analysis of retroperitoneal fat pad DNA from both trials indicated that apoptosis was increased (p < 0.01) by CLA consumption. Discussion: These results are interpreted to indicate that CLA consumption causes apoptosis in white adipose tissue. This effect occurs within 5 days of consuming a diet that contains CLA.     

Effect of a selectiveβ 2-adrenergic agonist (Cenbuterol) on energy balance and body composition in normal and protein deficient rats

In rats fed a normal (22% protein) diet, injection of clenbuterol (1 mg/kg/d for 21 d) did not affect energy intake, energy expenditure or weight gain, but reduced energetic efficiency, and fat and energy gains and increased body protein content. Presenting a low-protein (8%) diet reduced energy intake, gain and efficiency, body protein content and the mass of the gastrocnemius muscle when compared to rats fed the control diet. Injection of the protein-deficient rats with clenbuterol (1 mg/kg/d for 21 d) caused hypophagia and reduced body weight and energy gains, energy expenditure and total body fat. However, the total body content of protein was not significantly reduced and the percentage of body protein in this protein deficient, clenbuterol-treated group was greater than that of untreated rats on both the high- and low-protein diets. The ratio of body protein to fat following clenbuterol treatment was increased by over 50% in both normal and protein-deficient rats. The results show that in protein deficient animals, clenbuterol treatment may help conserve body protein at the expense of fat, resulting in a smaller, but leaner body mass.     

High Dietary Calcium Reduces Body Fat Content,Digestibility of Fat,and Serum Vitamin D in Rats

Objective: This study investigated which aspect of energy balance was responsible for the decrease in body fat content of rats fed a high‐calcium, high—dairy protein diet. Research Methods and Procedures: Male Wistar rats were fed a control diet (25% kcal fat, 14% kcal protein from casein, 0.4% by weight calcium) or high‐calcium diet (25% kcal fat, 7% kcal protein from nonfat dry milk, 7% kcal protein from casein, 2.4% calcium) for 85 days. Body weights, digestible energy intakes, energy expenditures, rectal temperatures, body composition, and serum glucose, insulin, free fatty acids, triglycerides, and 1, 25‐dihydroxyvitamin D were measured. Results: Rats fed high‐calcium diet gained significantly less weight than controls and had 29% less carcass fat. Gross energy intake was not significantly different between groups, but digestible energy was 90% of gross energy in the high‐calcium diet compared with 94% in the control diet because of increased fecal excretion of dietary lipid. The difference in digestible energy intake accounted for differences in carcass energy. Body temperatures and energy expenditures of the rats were not different. The high‐calcium diet reduced serum triglycerides by 23% and serum 1, 25‐dihydroxyvitamin D by 86%. Discussion: These results confirm that a high‐calcium diet decreases body weight and fat content due to a lower digestible energy intake caused by increased fecal lipid and a nonsignificant reduction in gross energy intake.     

Modulatory role of food, feeding regime and physical exercise on body weight and insulin resistance

Energy intake and expenditure is a highly conserved and well-controlled system with a bias toward energy intake. In times of abundant food supply, individuals tend to overeat and in consequence to increase body weight, sometimes to the point of clinical obesity. Obesity is a disease that is not only characterized by enormous body weight but also by rising morbidity for diabetes type II and cardiovascular complications. To better understand the critical factors contributing to obesity we performed the present study in which the effects of energy expenditure and energy intake were examined with respect to body weight, localization of fat and insulin resistance in normal Wistar rats. It was found that a diet rich in fat and carbohydrates similar to "fast food" (cafeteria diet) has pronounced implication in the development of obesity, leading to significant body weight gain, fat deposition and also insulin resistance. Furthermore, an irregularly presented cafeteria diet (yoyo diet) has similar effects on body weight and fat deposition. However, these rats were not resistant to insulin, but showed an increased insulin secretion in response to glucose. When rats were fed with a specified high fat/carbohydrate diet (10% fat, 56.7% carbohydrate) ad lib or at the beginning of their activity phase they were able to detect the energy content of the food and compensate this by a lower intake. They, however, failed to compensate when food was given in the resting phase and gained more body weight as controls. Exercise, even of short duration, was able to keep rats on lower body weight and reduced fat deposition. Thus, inappropriate food intake with different levels of energy content is able to induce obesity in normal rats with additional metabolic changes that can be also observed in humans.