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Biomedical subjects

Sandrine Wetzler

Publications and source records attributed to Sandrine Wetzler.

4 recordsLinked to original sources

Comparison of energy balance in two inbred strains of rats: Fischer F344 prone to obesity and Lou rats resistant to obesity.

This study aimed to compare energy balance, metabolic profiles and body composition between two inbred strains of rats (F344 and Lou) submitted to a self-selecting macronutrient. During the 3 weeks of experiment, the two strains did not differ significantly for their total energy intake; males: F344 = 5875.4 +/- 171.4 kJ, Lou = 5619.2 +/- 349.4 kJ; and females: F344 = 4058.8 +/- 118.7 kJ, Lou = 3864.4+/-166.4 kJ. However, F344 rats showed a higher weight gain, and percentage of total fat tissue, together with a lower percentage of carcass weight than Lou rats regardless of sex. The percentages of each macronutrient revealed a lower preference of protein for F344 males and the opposite in females for CHO. The thermogenic activity measured in interscapular brown adipose tissue was lower in Fischer than in Lou while the reverse was observed for leptinemia and insulinemia. These results indicate that the mechanism responsible for the regulation of body composition observed in Lou rats takes place very early in life and attest the interest in this strain for studying the features of resistance to obesity.

Adipose Tissue↗

In vivo leptin infusion impairs insulin and leptin signalling in liver and hypothalamus.

Leptin resistance contributes to the pathogenesis of common obesity related metabolic diseases, including insulin resistance. However, the relationship between leptin and insulin resistance is not clearly established. Here, we show that induced hyperleptinemia by leptin infusion alters insulin signalling in rat liver. Leptin infusion clearly reduced the insulin or leptin dependent IRS-1/IRS-2 association to p85 regulatory subunit of PI 3-kinase. Leptin infusion also abolished STAT-3 phosphorylation in response to insulin or leptin and similar results were obtained for MAP-kinase phosphorylation. Hypothalamic leptin resistance was also induced by leptin infusion since leptin was unable to induce STAT-3 phosphorylation. These results provide evidence that induced hyperleptinemia can contribute to the onset of insulin resistance at least at the hepatic level.

Animals↗

Acute third ventricular administration of leptin decreases protein and fat in self-selecting rats.

The peripheral administration of leptin reduces food intake (FI) body weight gain (BWG) and modifies food choice. The aim of this study was to examine the effect of acute cerebral injections of leptin on food selection in rats. Male rats were first adapted to the food choice paradigm (protein, carbohydrate, fat) for 3 weeks. They were then implanted with a cannula in the third ventricle. Leptin (leptin group=L) or saline (control group=C) injections were performed at either the beginning or the end of the night at 4-day intervals. FI was recorded continuously, 3 days before, during and then after injections. Rats were sacrificed 86 h after the second injection. After both injections, BWG and FI were reduced. The reduction in FI concerned only nocturnal intake, whatever the timing of the injection. When the injection was given at the beginning of the night, the reductions after a 1-h latency period were -45% and -27.5% during the first and second days, respectively. Following the second injection, the same effects were observed immediately (-16% and -41%, respectively). Only the fat and protein intakes were significantly reduced. This lower FI was due to a reduction in meal size and duration. The reduction resulted in a lower BWG and total white adipose tissue mass. At the time of sacrifice, 6 h after food deprivation, leptinemia and insulinemia were reduced in leptin-treated rats. Glycemia values were identical. It was thus demonstrated that central leptin was a satiation factor rather than a satiety factor.

Animal Feed↗

Intraperitoneal leptin modifies macronutrient choice in self-selecting rats.

This study aimed to evaluate the consequences on food intake and body weight (BW) of leptin administration in rats receiving a choice between the three macronutrients. Two studies were performed: during the first, rats received an acute intraperitoneal (IP) leptin administration (1 mg/kg) twice (at 8 and 14 weeks of age), at the beginning of the nocturnal cycle, while during the second, they received a chronic leptin infusion (osmotic minipump, 7 days). The total 24-h food intake after acute leptin injections was reduced by 14% and 17%, respectively. Body weight gain (BWG) after leptin injections was about half that seen on control days. Chronic leptin infusion reduced total intake, affecting mainly protein (P). Fat intake increased slightly since day 2 and became significant on the fourth day. After the leptin infusion, carbohydrate (CHO) eaters (>35% carbohydrate/total energy) significantly reduced the carbohydrate proportion in their total energy intake. There was no difference concerning macronutrient selection by fat eaters (Hfat). Leptin infusion reduced the number of mixed meals on the first day. In addition, the thermogenesis of brown adipose tissue (BAT) was higher in leptin than in control (C) rats. Consequently, leptin injections reduced food intake and BWG and increased thermogenesis, thus acting on the two terms of the energy balance. Moreover, leptin has different effects on macronutrient preferences, dependent upon age (tests 1 and 2) and the type (acute or chronic) of injection. High leptinemia level related to age or to minipump infusion lead to leptin resistance as found in old or obese subjects. It could explain our results.

Adipose Tissue, Brown↗