Michael Pellizzon

Differential effects of fatty acids and exercise on body weight regulation and metabolism in female Wistar rats.

High-fat diets made with different fats may have distinct effects on body weight regulation and metabolism. In the present study, the metabolic effects of high-fat (HF) diets made with fish oil, palm oil, and soybean oil were compared with a low-fat diet in female Wistar rats that were either exercised (EX, swimming) or that remained sedentary as controls. Each adult rat was exposed to the same diet that their dams consumed during pregnancy and lactation. When they were 9 weeks old, rats began an EX regimen that lasted for 6 weeks. Twenty-four hours after the last EX bout, rats were sacrificed in a fasted state. It was observed that HF feeding of soybean oil induced more body weight and fat gain, as well as insulin resistance, as indicated by insulin/glucose ratios, than other oils. Female rats fed a HF diet made with fish oil had body weight and insulin sensitivity not different from that observed in low fat fed control rats. For rats fed HF diets made with soybean oil or palm oil, EX also exerted beneficial effects by reducing body fat %, blood insulin, triglyceride and leptin levels, as well as improving insulin sensitivity.

Short-term weight cycling in aging female rats increases rate of weight gain but not body fat content

OBJECTIVE: To examine the effects of short-term repeated weight cycling (WC) above and below the baseline (BL) body weight (BW) on body weight regulation, feeding efficiency, and fat content in old female Wistar rats when dietary fat content was kept constant.DESIGN: Completely randomized.ANIMALS AND METHODS: Female Wistar rats, 11 months old at the beginning of the study, were randomly divided into six groups (12 per group) after a group of rats (BL) was sacrificed for baseline data collection: the high fat gain (HFG) group gained weight to 20% above the BL weight with a high fat diet (HF) and returned to BL level by food restriction (50% of ad-libitum amount) for five cycles; the high fat loss (HFL) group lost weight to 20% below the BL weight by food restriction (50% of ad-libitum amount) and regained to BL level by ad-libitum feeding for four cycles; the high fat ad-libitum (HFA) and low fat ad-libitum (LFA) groups were fed HF and low fat (LF) diet, respectively, ad-libitum for the entire study; the high fat restricted (HFR group) and low fat restricted rats (LFR group) were fed the HF and LF diet, respectively, in restricted amounts to maintain BW at BL level.RESULTS: A trend of increased rates of weight gain and feeding efficiencies from the first to last cycles for both WC groups was observed, and significant increases was observed between cycles 4 and 5. The rate of weight gain and feeding efficiency of HFL was significantly higher than that of the HFG group for all cycles (P<0.05). The rates of weight loss were significantly decreasing with each successive cycle for HFG, but were unchanged for HFL. Percentage of body fat was not modified permanently from BL to sacrifice for both HFG and HFL groups. The body fat of HFA was higher than that of the other groups (P<0.01), while the body fat of LFA was significantly higher than that of the LFR, BL and HFL groups (P<0.01), but was similar to that of the HFG and HFR groups. The body fat of WC groups and HFR were similar to each other. The percentage of internal fat (retroperitoneal+omental) were similar for the WC groups. The percentage of internal fat of the HFG, HFR and LFA groups were similar, but were significantly higher than that of the BL and LFR groups (P<0.05). The percentage of internal fat of HFA was significantly higher than that of the rest of the groups (P<0.01).CONCLUSION: Short-term WC did not affect body fat content in these animals, but since weight gain became easier and weight loss became more difficult for animals in the HFG group, repeated WC may promote obesity in these rats.

Endogenous and diet-induced hypercholesterolemia in nonhuman primates: effects of age, adiposity, and diabetes on lipoprotein profiles.

Nonhuman primates (NHPs) share with humans many features of lipid metabolism and often develop all features of the metabolic syndrome, including hypertriglyceridemia and low high-density lipoprotein cholesterol, and have been used in many studies of potential therapeutics during the preclinical phase. Here we identify for the first time in middle-aged and older rhesus the natural occurrence of hypercholesterolemia, and this hypercholesterolemia develops despite maintenance on a low-cholesterol diet. The aims of this study were to (a) define normal and hypercholesterolemia in rhesus monkeys, (b) determine the factors associated with the development of hypercholesterolemia, (c) compare the lipoprotein profiles in adult rhesus monkeys fed a low-fat/low-cholesterol diet (LFLC) with the profiles of human subjects, and (d) determine the effect of a 16-week high-fat/high-cholesterol (HFHC) diet feeding on total cholesterol and lipoprotein profiles in middle-aged and older monkeys. In our colony, maintained on a constant diet with negligible cholesterol, the mean total cholesterol level in healthy nondiabetic monkeys was 3.7 ± 0.02 mmol/L, with hypercholesterolemia identified as the 95th percentile of the normal cholesterol distribution (≥5.2 mmol/L). Severe hypercholesterolemia developed in the HFHC-fed group; however, despite the high-fat diet composition, unexpectedly, no weight gain occurred in these NHPs. The diet-induced hypercholesterolemia differed significantly in lipoprotein pattern from that of the spontaneous hypercholesterolemia. In summary, despite ingesting only a LFLC, NHPs frequently develop hypercholesterolemia, reflecting lipoprotein patterns similar to human subjects; and this lipid profile of spontaneous hypercholesterolemia differs significantly from the hypercholesterolemia induced by an HFHC diet.

Prenatal Cocaine, Alcohol, and Undernutrition Differentially Alter Mineral and Protein Content in Fetal Rats

Alcohol exposure and undernutrition during pregnancy have been associated with altered fetal body composition. Recent observations suggest that cocaine exposure during pregnancy may impair delivery of nutrients to the fetus and could thereby alter body growth and composition. Such effects are important because they can adversely influence physical and neural development. Consequently, we investigated the dose-dependent effects of cocaine on fetal body composition in an animal (rat) model and compared such effects with those caused by prenatal alcohol exposure and undernutrition. Pregnant Sprague-Dawley rats received either 20, 30, 40, or 50 mg/kg cocaine HCl (SC) twice daily from gestation days 7 through 19. Pair-fed (undernutrition) and untreated control groups and a group receiving 3.0 g/kg alcohol (PO) twice daily served as comparison groups (n = 11 to 14/group). Females were sacrificed on gestation day 20. One male and one female fetus was removed from each dam. The fetuses were minced, dehydrated, defatted, and analyzed for content of protein and the minerals Zn, Ca, Fe, Mg, K, and Na. In terms of concentration per unit of fat-free dry solids, male fetuses in the cocaine groups showed significant decreases in protein compared to untreated controls (15+/-3 to 20+/-2 mg/g vs. 24+/-4 mg/g, p = 0.01). There was a significant treatment effect for Ca (p < 0.05), reflecting a trend for decreased Ca concentrations in the fetuses of the cocaine and undernutrition groups. Male fetuses in the alcohol group had significantly elevated Mg levels compared to male fetuses in the other groups (3.0+/-0.8 vs. 1.0+/-0.2 to 2.3+/-0.7 mg/g, p < 0.05). There were some sex differences, with female fetuses having significantly lower concentrations of Mg, Fe, K, and higher protein concentrations than male fetuses. Although the effects were few and modest, these results suggest that prenatal cocaine, alcohol, and undernutrition can differentially alter fetal body weight and composition and, therefore, adversely influence fetal development.

Conjugated linoleic acid does not impair fat regain but alters IGF-1 levels in weight-reduced rats

It has been previously reported that in rats undergoing repeated weight gain/loss cycles, more fat is regained than that was lost. Conjugated linoleic acid (CLA), a collective name for a mixture of positional and geometrical isomers of linoleic acid, is known to regulate body composition by decreasing body fat. The present study was designed to examine the effects of CLA on body fat regain in weight-reduced obese rats. Female Wistar rats (n=52), 6 mo old, were divided into 4 groups: 1) HFRF rats (n=10) were fed a high fat diet (40% ww) diet for 9 weeks to an obese state and were then food restricted (50% ad-lib) with a modified high fat diet for 3 weeks to induce a 20% body weight loss. They were then refed the high fat diet ad-lib for 8 weeks; 2) HFCL rats (n=22) were treated in the same manner as rats in HFRF except were refed a high fat diet with 1% CLA (ww); 3) LFCN rats (n=10) were fed regular rodent diet ad-lib; 4) HFCN rats (n=10) were fed a high fat diet ad-lib. Ten HFCL rats were sacrificed after 4 weeks of refeeding while body composition and plasma glucose and insulin assessed for the other groups as a comparison. All remaining rats were sacrificed after 8 weeks of refeeding. After 4 weeks of refeeding, HFCL rats were similar in both body weight and body fat %. At the end of the study, HFCL rats weighed the same as high fat fed rats while HFRF rats weighed the same as rats of the other groups. All high fat fed groups had significantly higher % body fat than low fat fed rats but were not different from each other (HFCL: 22 ± 2%; HFRF: 23 ± 2%; HFCN: 27 ± 2%; LFCN: 15 ± 2%). HFCL and HFCN rats had significantly higher retroperitoneal lipoprotein lipase activity levels than that of HFRF rats (p<0.05). HFRF and HFCL rats had similar plasma insulin, leptin, and estradiol levels at sacrifice. HFCL rats had significantly lower IGF-1 levels (p<0.05) than that of HFRF and HFCN rats, while LFCN rats had levels similar to all groups (nmol/L, HFCL: 10 ± 0.7; HFRF: 13 ± 0.8; HFCN: 13 ± 0.8; LFCN: 11 ± 1.7). We conclude that a 40% high fat diet with 1% CLA fed to weight-reduced obese rats did not prevent the fat regain during the refeeding phase. The previously reported anticarcinogenic effect of CLA reported by other investigators may be partially due to lowered IGF-1 levels without the alteration of other hormone levels.

Effect of a modified milk fat and calcium in purified diets on cholesterol metabolism in hamsters

Modification of milk fat both by partially replacing saturated FA with oleic acid (18∶1) and by increasing calcium intake independently reduces plasma cholesterol. Whether modification of both factors together would synergistically reduce plasma cholesterol is unknown. Seventy-two male golden Syrian hamsters were separated into four diet treatment groups (n=18/group) and fed ad libitum for 7 wk. Diets contained either modified milk fat (MMF) or regular milk fat (RMF) with either 0.5% (MMF and RMF) or 1.3% calcium (w/w) (MMFC and RMFC). All diets contained 11% test fat, 4% soybean oil, and 0.15% cholesterol (w/w). During the last week, feces were collected for three consecutive days for analysis of fecal FA, cholesterol, and calcium excretion. Overnight-fasted animals were sacrificed, and plasma and livers were collected for lipid analysis. Neither MMF nor additional calcium significantly affected plasma lipids. However, significant interactions existed between MMF and additional calcium for the ratio of LDL cholesterol to HDL cholesterol (LDL/HDL), indicating that increased calcium intake reduced this ratio only in RMF animals. In addition, MMF reduced LDL/HDL relative to RMF. MMF significantly increased hepatic total and esterified cholesterol. Additional calcium significantly increased fecal calcium and saturated FA (SFA) excretion, whereas MMF significantly reduced SFA excretion. RMFC induced the highest excretion of 16∶0 among all groups. Replacement of SFA with 18∶1 in the MMF reduced the impact of high calcium on LDL/HDL. Additional calcium reduced LDL/HDL only in the presence of RMF, which may be achieved through an increased excretion of 16∶0.