Adaptation to lactation in OLETF rats lacking CCK-1 receptors: body weight, fat tissues, leptin and oxytocin

Abstract

Objective: To understand the adaptation to lactation of obese rats, by studying the interplay among the gut hormone cholecystokinin (CCK), the adiposity hormone leptin and the affiliation hormone oxytocin in modulating body mass and fat storage. Design: Strain differences were examined between Otsuka Long Evans Tokushima Fatty (OLETF) rats lacking expression of functional CCK-1 receptors and Long Evans Tokushima Otsuka (LETO) controls, tested as nulliparous dams, at the 7 and 15th lactation day, at weaning (lactation day 22) or 8 weeks postweaning. Measurements: We measured body mass, fat pads (brown, retroperitoneal and inguinal) and inguinal adipocytes. Plasma levels of leptin and oxytocin were determined. Results: Fat depots of LETO female rats were larger during lactation compared to the levels found in postweaning and nulliparous female rats. LETO female rats gained weight and accumulated fat during pregnancy and lactation, returning to their normal fat levels postweaning. In contrast, OLETF female rats presented lower body weight and fat depots during the lactation period than nulliparous dams, and regained the weight and fat postweaning. Plasma leptin and oxytocin were highly correlated and followed the same pattern. OLETF leptin levels were highly correlated with fat depot and inguinal cell surface. No significant correlation was found for LETO parameters. Conclusions: Pregnancy and lactation are energy-consuming events, which naturally induce female rats to increase food intake and accumulate fat. When challenged by the demands of rapidly growing preobese OLETF pups, OLETF dams' fat stores are reduced to lean, LETO levels. During lactation, sensitivity of the oxytocinergic neurons descending from the paraventricular nuclei to the nucleus of the solitary tract to CCK is reduced. We theorized that this pathway is not available to OLETF female rats that lack functional CCK-1 receptors to mediate the signal. The current study contributes to the understanding of the female body's adaptation to lactation.

Toward an animal model of childhood-onset obesity: follow-up of OLETF rats during pregnancy and lactation

“…Interestingly, whereas OLETF dams gained significantly more weight during pregnancy, the lactating period represented a time point where OLETF females gradually lost weight, almost reaching weight levels of LETO dams at the time of weaning. We have recently reported that this weight loss throughout lactation is accompanied by a decrease in fat stores, adipocyte cell size, and leptin levels (49). We can only speculate about why OLETF females do not maintain a relative hyperphagia beyond that shown by lactating controls during such an energy-demanding period.…”

“…Representative cells chosen presented a smooth and clear membrane, with no granulation around. A similar methodological approach was described elsewhere (31,49). The estimated number of cells per fat pad was calculated with the average cell diameter, a density conversion factor (0.915 g/cc), and the mass of the fat pads, as previously described (3,32).…”

“…Beyond the increased nursing time found in the OLETF strain, we have recently reported a detailed physiological characterization of the changes dams of both strains undergo throughout lactation (49). OLETF females appear to gradually loose weight and body fat after delivery, an outcome that hypothetically might be a consequence of larger milk production to feed hyperphagic pups.…”

Development of obesity in the Otsuka Long-Evans Tokushima Fatty rat

“…Representative cells chosen presented a smooth and clear membrane, without surrounding granulations. A similar methodological approach was described elsewhere (31,57). The estimated number of cells per fat pad was calculated using the average diameter, a density conversion factor (0.915 g/cc), and the mass of the fat pads, as previously described (3,32).…”

Oxytocin and bone status in men: analysis of the MINOS cohort

“…OT is a neuropeptide predominantly synthesized within magnocellular neurons of the hypothalamus, but also in some peripheral tissues, including the reproductive system, heart, and bone [2]. OT secretion is modulated by several factors, including estrogens, testosterone, and leptin [2][3][4]. Subcutaneous OT injection reverses bone loss in ovariectomized mice, and enhances bone microarchitecture and biomechanical strength [5].…”