Anne Buison

Obesity due to high fat diet decreases the sympathetic nervous and cardiovascular responses to intracerebroventricular leptin in rats

Obesity is associated with an increase in plasma leptin levels primarily derived from enhanced expression of the leptin gene in the adipose tissue. Leptin levels and expression are higher in females than males. The main functions of leptin are to decrease food intake and increase sympathetic nerve activity, especially in the brown adipose tissue. The high levels of leptin in obese, female rats suggest leptin resistance. In this article we describe experiments designed to investigate the effect of the intracerebroventricular (i.c.v.) administration of leptin on lumbar sympathetic nerve activity (LSNA) and cardiovascular parameters in female rats fed a low fat diet (control), a high fat diet (obese), or high fat diet followed by a period of food restrictions (reduced). The i.c.v. leptin administration increased LSNA in control rats, but decreased it in obese rats. In weight reduced animals the LSNA response to leptin returned to control levels. The i.c.v. leptin increased the mean arterial pressure in control and wt. reduced rats, but not in obese animals. The heart rate did not respond to leptin in any animal group. These results suggest that obesity decreases the central nervous system (CNS)-mediated lumbar sympathetic nervous and cardiovascular responses to leptin and that these responses recover following food restriction and wt. reduction. We conclude that obesity is associated with a decreased CNS response to leptin leading to a decrease in leptin effects to increase the activities of the autonomic nervous and cardiovascular systems.

Leptin resistance in obesity is characterized by decreased sensitivity to proopiomelanocortin products

Obesity in normal animals has been demonstrated to be associated with a decrease in sensitivity to leptin especially as it relates to leptins capacity to increase sympathetic nerve activity and enhance cardiovascular dynamics. In normal animals leptin has been demonstrated to exert significant regulatory responses by its capacity to increase proopiomelanocortin (POMC) expression and especially the increase in alpha melanocyte stimulating hormone (alphaMSH). These responses to leptin are blocked by a melanocortin-4 (MC-4) receptor antagonist. In this study we investigated the responsiveness of the sympathetic nervous system and cardiovascular system of high fat fed obese animals to the intracerebroventricular (ICV) administration of the POMC products alphaMSH and beta-endorphin (beta-END). We further investigated these responses in obese animals following leptin administration in the presence of MC-4 receptor and opioid receptor blockade. The ICV administration of leptin resulted in an increase in lumbar sympathetic nerve activity (LSNA) and mean arterial pressure (MAP) in normals but decreased it in the obese. The ICV administration of alphaMSH increased the LSNA and MAP in normal animals but to a lesser degree in obese animals. On the other hand beta-endorphin decreased the LSNA and MAP in normal animals but increased it in obese animals. Additionally ICV leptin administration in obese animals in the presence of MC-4 or opioid receptor blockade resulted in an increase in sympathetic activity and a pressor response. From these studies we conclude that obesity in high fat fed animals is characterized by a decreased sensitivity to alphaMSH and a paradoxical response to beta-endorphin and this altered responsiveness may be a factor in the altered leptin resistance characteristic of obese animals.

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.

High-fat feeding of different fats during pregnancy and lactation in rats: Effects on maternal metabolism, pregnancy outcome, milk and tissue fatty acid profiles

This study was designed to examine the effects of consumption of different fats during pregnancy and lactation on maternal metabolism, pregnancy outcome, and milk and tissue fatty acid (FA) profiles. Wistar rats were divided into three groups according to dietary fat source: PM (40% crude palm oil), n = 7; SB (40% soybean oil), n = 7; and VS (40% partially hydrogenated vegetable shortening), n = 8. Rats were fed experimental diets from day 1 of pregnancy to sacrifice, which was one week after weaning of pups (21d). Milk was expressed from dams on day 14 of lactation. PM, SB and VS milk samples had the same fat content and had FA profiles similar to that of their respective diets. SB and VS dams had significantly more pups dead at birth compared to PM dams. One week after weaning of pups, PM dams had significantly higher triglyceride levels compared to all other groups (PM = 2.08 ± 0.27 mmol/L; SB = 0.88 ± 0.10 mmol/L; VS = 0.78 ± 0.08 mmol/L, p<0.05). PM dams may have slower triglyceride clearance, making hypertriglyceridemia apparent post-weaning. Retroperitoneal adipose tissue and carcass FA profiles of dams positively reflected the FA content of the respective diets. Such influence of diet on milk, adipose tissue and carcass FA content may thus alter metabolic processes during and following pregnancy and lactation and may also affect offspring growth and development via differences in milk composition.

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.

Long-term effects of exogenous leptin on body weight and fat in post-obese female rats.

This study was designed to test the hypothesis that short-term leptin infusion during the post-obese refeeding phase of weight-reduced rats would reduce the rate of weight regain and, as a result, reduce the final body weight and fat content in weight-reduced rats. Ninety-six female Wistar rats were divided into four groups: (1) LFCON (low-fat control) group: Rats in this group were fed the control low-fat (LF) diet ad lib for the entire study period. (2) HFCON (high-fat control) group: Rats in this group were fed the high-fat (HF, 40% fat) diet ad lib for the study period. (3) HFRLP (high-fat fed, weight-reduced, leptin treatment) group: Obese rats in this group were weight-reduced and received leptin infusion for 2 weeks (miniosmotic pumps, 0.5 microg/kg/day) during the post-obese refeeding period. (4) HFRSM (high-fat fed, weight-reduced, sham control) group: Rats in this sham-control group were treated the same as the rats in the HFRLP group with the exception that no leptin was actually infused during the first 2 weeks of refeeding period. The results demonstrated that 2 weeks of leptin treatment during the early refeeding phase did not prevent weight regain in weight-reduced rats, but it significantly reduced body fat content in these rats as compared to ad lib fed obese control rats. One cycle of weight reduction and regain did not alter the body weight and body fat content in HFRSM rats when compared to obese control rats. Therefore, leptin treatment was effective in reducing body fat content in post-obese rats for up to 7 weeks, but the long-term effect of short-term leptin treatment needs to be further examined.

Differential Gender Response Produced by Meal and Ad Lib Feedings of a High-Fat Diet in Osborne-Mendel Rats

We investigated if there were gender differences in metabolic consequences produced by meal feeding of a high-fat (HF) diet in male and female Osborne-Mendel rats. An HF diet was fed either ad lib (AL) or in 1 meal (MF) during the last 3 h of the dark cycle for 4 weeks (lights off from 2400 h to 1200 h). All rats were sacrificed at 1 of 3 time-points: prior to MF rats receiving their food at 0900 h, after food was taken from MF groups at 1200 h or 1500 h. Food intake, body weight, body fat weight, retroperitoneal adipose tissue lipoprotein lipase activity, plasma cholesterol, or HDL-cholesterol levels did not differ between MF- and AL-fed groups, but were higher in male than in female rats. There were no differences between the male and female groups in plasma levels of insulin and glucose or systolic blood pressures. Plasma triglyceride levels at 1200 h were significantly different between MF and AL Groups within either gender, but this was not observed at 0900 h or 1500 h. Body weights were correlated with internal fat weights and plasma cholesterol levels in both males (r = 0.57, p < 0.05) and females (r = 0.59, p < 0.05). Hence, it is the amount of HF diet ingested, rather than the pattern of meal feeding, that was the most significant factor related to gender differences in weight gain, increases in fat mass, and metabolic differences.

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.