RESUMEN
The childhood obesity epidemic continues to be a challenge. Maternal obesity and excessive infant weight gain are strong predictors of childhood obesity, which itself is a major risk factor for adult obesity. The primary source of nutrition during early life is breast milk, and its composition is impacted by maternal habitus and diet. We thus studied the relationship between maternal BMI, serum lipids and insulin, and breast milk fat and calorie content from foremilk to hindmilk. Women who were exclusively breastfeeding at 7-8 weeks postpartum were BMI classified as Normal (18.5-24.9, n = 9) and women with Overweight/Obese (OW/OB ≥ 25, n = 13). Maternal blood and continuous breast milk samples obtained from foremilk to hindmilk were analyzed, and infant milk intake was assessed. Women with OW/OB had significantly higher milk fat and calorie content in the first foremilk and last hindmilk sample as compared to Normal BMI women. Amongst all women, maternal serum triglycerides, insulin, and HOMA were significantly correlated with foremilk triglyceride concentration, suggesting that maternal serum triglyceride and insulin action contribute to human milk fat content. As the milk fat content of OW/OB women has caloric implications for infant growth and childhood obesity, these results suggest the potential for modulating milk fat content by a reduction in maternal serum lipids or insulin.
RESUMEN
The maintenance of mitochondrial activity in hypothalamic neurons is determinant to the control of energy homeostasis in mammals. Disturbs in the mitochondrial proteostasis can trigger the mitonuclear imbalance and mitochondrial unfolded protein response (UPRmt) to guarantee the mitochondrial integrity and function. However, the role of mitonuclear imbalance and UPRmt in hypothalamic cells are unclear. Combining the transcriptomic analyses from BXD mice database and in vivo experiments, we demonstrated that physical training alters the mitochondrial proteostasis in the hypothalamus of C57BL/6J mice. This physical training elicited the mitonuclear protein imbalance, increasing the mtCO-1/Atp5a ratio, which was accompanied by high levels of UPRmt markers in the hypothalamus. Also, physical training increased the maximum mitochondrial respiratory capacity in the brain. Interestingly, the transcriptomic analysis across several strains of the isogenic BXD mice revealed that hypothalamic mitochondrial DNA-encoded genes were negatively correlated with body weight and several genes related to the orexigenic response. As expected, physical training reduced body weight and food intake. Interestingly, we found an abundance of mt-CO1, a mitochondrial DNA-encoded protein, in NPY-producing neurons in the lateral hypothalamus nucleus of exercised mice. Collectively, our data demonstrated that physical training altered the mitochondrial proteostasis and induced the mitonuclear protein imbalance and UPRmt in hypothalamic cells.
