Bromocriptine treatment at the end of lactation prevents hyperphagia, higher visceral fat and liver triglycerides in early‐weaned rats at adulthood

Abstract

Non-pharmacological early weaning (NPEW) leads offspring to obesity, higher liver oxidative stress and microsteatosis in adulthood. Pharmacological EW (PEW) by maternal treatment with bromocriptine (BRO) causes obesity in the adult progeny but precludes hepatic injury. To test the hypothesis that BRO prevents the deleterious changes of NPEW, we injected BRO into the pups from the NPEW model in late lactation. Lactating rats were divided into two groups: dams with an adhesive bandage around the body to prevent breastfeeding on the last 3 days of lactation and dams whose pups had free suckling (C). Offspring from both groups were subdivided into two groups: pups treated with BRO (intraperitoneal (i.p.) 4 mg/kg per day) on the last 3 days of lactation (NPEW/BRO and C/BRO) or pups treated with the vehicle (NPEW and C). At PN120, offspring were challenged with a high fat diet (HFD), and food intake was recorded after 30 minutes and 12 hours. Rats were killed at PN120 and PN200. At PN120, adipocyte size was greater in the NPEW group but was normal in the NPEW/BRO group. At PN200, the NPEW group presented hyperphagia, higher adiposity, adipocyte hypertrophy, hyperleptinaemia, glucose intolerance and increased hepatic triglycerides. These parameters were normalized in the NPEW/BRO group. In the feeding test, BRO groups showed lower HFD intake at 30 minutes than did their controls; however, at 12 hours, the NPEW group ate more HFD. The treatment with BRO can preclude some deleterious effects of the NPEW model, which prevented the development of overweight and its comorbidities.

Does early weaning shape future endocrine and metabolic disorders? Lessons from animal models

“…93,94 In addition, early bromocriptine exposure attenuated hyperphagia and increased adiposity and hyperleptinemia in NPEW offspring. 113 These observations highlight the deleterious impact of isolated breast milk restriction on liver metabolism, reinforcing the effects of early weaning on the hepatic gene expression profile and function throughout life. 65 Although these models mimic the human conditions of early weaning by promoting early life breast milk restriction and the thrifty phenotype throughout life, the hepatic outcome is not the only difference between adult PEW and NPEW offspring.…”

“…Indeed, the NPEW offspring treated with bromocriptine during the last 3 d of lactation were protected from steatosis and glucose intolerance. 113 The beneficial effects of bromocriptine on the liver were described before in adult animals. 93,94 In addition, early bromocriptine exposure attenuated hyperphagia and increased adiposity and hyperleptinemia in NPEW offspring.…”

Effect of soybean milk fermented with Lactobacillus plantarum HFY01 isolated from yak yogurt on weight loss and lipid reduction in mice with obesity induced by a high-fat diet

“…Fat accumulation develops into chronic inflammation of fatty liver, although it can be reversed and recovered by fat metabolism; however, if diets and lifestyle habits are not modified, fatty liver inflammation may worsen and develop into liver fibrosis, cirrhosis, or liver failure. 27 Studies have shown that l -carnitine treatment can effectively reduce the fat accumulation and fat cavities, as well as reduce the TG content in the liver. 28 The organ index can reflect the health status of the mice, and the body fat rate can directly reflect fat content in mice, that is, the degree of obesity.…”

Hepatic lipid metabolism in adult rats using early weaning models: sex-related differences

“…27 Peixoto-Silva et al (2017) showed that BRO treatment of the pups during the last 3 days of lactation prevents the hepatic fat accumulation associated with an improvement in adiposity at adulthood, but in a dose 4 times higher than the administrated to the dams (4 mg/kg per day). 28 Thus, in the PEW model, both maternal lower PRL levels and BRO (even in small quantities) could be responsible for the programming of the liver function in the adult male offspring. Therefore, considering the unexpected effects of BRO on the liver function of male offspring programmed by EW during the critical window of breastfeeding, in the present study, our primary aim was to assess morphological parameters of the liver tissue as well as main molecular pathways associated with hepatic metabolism to better understand the underlying mechanisms responsible for the altered function in each of the EW models (PEW and NPEW) used in our laboratory.…”