Leptin injections following a weight reduction in diet-induced obese rats do not prevent weight and fat regain and cause metabolic alterations

This study examined whether leptin (LP) injections following a weight reduction in diet-induced obese rats would reduce both the enhanced food intake and body weight (BW) regain typically seen in weight reduced animals after a weight reduction. Also, the findings of the current study were compared to a study using a LP infusion in a similar study design to that of the current study to determine which method is the most efficacious and beneficial ( Physiol Behav 74: 321–328). Finally, the current study examined plasma F₂-isoprostane (ISO) levels to determine whether a high fat (HF) diet in addition to this weight reduction model and LP treatment may influence oxidant status. Female Wistar rats (n = 100, n = 20/group) were divided into 5 groups: (1) HFCL rats were fed a HF diet (35% w/w) for 8 wks to an obese state and were then food restricted (50% ad-lib) with a fortified HF diet for 2 wks to induce a 20% BW loss. They were then given LP injections (200μg/kg BW, twice daily, IP) for 19d concomitant with being refed the HF diet ad-lib for 11 wks; (2) HFCS rats were treated in the same manner as HFCL rats except that they were given saline injections during refeeding; (3) HFCPS rats were treated like HFCS rats except that they were pair-fed with the HFCL rats; (4) HFA rats were fed HF diet ad-lib; (5) LFA rats were fed a low fat diet (AIN-93M) ad-lib. Ten rats from each group were sacrificed after LP treatment and at the end of the study. Food and caloric intakes were monitored, and body composition and plasma glucose, insulin, and LP levels were assessed at sacrifice periods. LP injections given to diet-induced obese rats after a weight reduction to prevent weight and fat regain caused temporary insulin resistance and hyperinsulinemia. LP resistance was evident after one wk of treatment in this study. LP treatment had no effect on body fat content both short-term and tong-term, but it reduced carcass protein content and % protein/% fat ratios, which persisted until the end of the study. Bolus LP injections to manipulate LP circadian rhythm were ineffective in influencing food intake, BW and body fat content. Compared to our previous LP infusion study using a similar study design to prevent weight and fat regain, it is evident that an infusion of a continuous low dose of LP was more efficacious than bolus LP injections in affecting body composition. Finally, LP treatment in this model did not influence ISO levels, but this needs review since the kit we used may not yield an accurate measure of this metabolite. Thus, insulin resistance induced by LP treatment in weight-reduced HF fed rats may reduce protein synthesis while keeping fat mass. Hence, this may imply that LP treatment may not be beneficial to obese rats with insulin resistance and without diet modifications.