Supplementation of polar lipids-enriched milk fat globule membrane in high-fat diet-fed rats during pregnancy and lactation promotes brown/beige adipocyte development and prevents obesity in male offspring.

Promoting brown adipose tissue (BAT) function or browning of white adipose tissue (WAT) provides a defense against obesity. The aim of the study was to investigate whether maternal polar lipids-enriched milk fat globule membrane (MFGM-PL) supplementation to high-fat diet (HFD) rats during pregnancy and lactation could promote brown/beige adipogenesis and protect against HFD-induced adiposity in offspring. Female SD rats were fed a HFD for 8 weeks to induce obesity and, then, fed a HFD during pregnancy and lactation with or without MFGM-PL. Male offspring were weaned at postnatal Day 21 and then fed a HFD for 9 weeks. MFGM-PL treatment to HFD dams decreased the body weight gain and WAT mass as well as lowered the serum levels of insulin and triglycerides in male offspring at weaning. MFGM-PL+HFD offspring showed promoted thermogenic function in BAT and inguinal WAT through the upregulation of UCP1 and other thermogenic genes. In adulthood, maternal MFGM-PL supplementation reduced adiposity and increased oxygen consumption, respiratory exchange ratio, and heat production in male offspring. The enhancement of energy expenditure was correlated with elevated BAT activity and inguinal WAT thermogenic program. In conclusion, maternal MFGM-PL treatment activated thermogenesis in offspring, which exerted long-term beneficial effects against HFD-induced obesity in later life.

Li T ，Gong H ，Yuan Q ，Du M ，Ren F ，Mao X ... -  《-》

Milk fat globule membrane and its component phosphatidylcholine induce adipose browning both in vivo and in vitro.

The functional induction of brown-like adipocytes in white adipose tissue (WAT) provides a defense against obesity. The aim of this study was to analyze the effects of milk fat globule membrane (MFGM) and its component phosphatidylcholine (PC) on the brown remodeling of WAT. Male C57BL/6 J mice were fed a high-fat diet (HFD) for 8 weeks and then fed HFD for another 8 weeks with MFGM. In vitro studies were performed in C3H10T1/2 pluripotent stem cells, 3T3-L1 pre-adipocytes and differentiated inguinal WAT stromal vascular cells (SVCs) to determine the role of MFGM and PC on the formation of brown-like adipocytes. MFGM decreased fasting glucose and serum insulin levels in HFD-fed mice. MFGM improved glucose tolerance and insulin sensitivity, and induced browning of inguinal WAT. MFGM and its component PC stimulated transformation of brown-like adipocytes in C3H10T1/2 pluripotent stem cells, 3T3-L1 adipocytes and SVCs by increasing the protein expression of UCP1, PGC-1α, PRDM16 as well as the mRNA expression of other thermogenic genes and beige cell markers. MFGM and PC also increased mitochondrial DNA (mtDNA) copy number, mitochondrial density and oxygen consumption rate and up-regulated the mRNA expression of mitochondria-biogenesis-related genes in vitro. PPARα inhibitor GW6471 treatment or knockdown of PPARα using lentivirus-expressing shRNA inhibited the PC-induced increase in the protein expression of UCP1, PGC-1α and PRDM16 in C3H10T1/2 pluripotent stem cells and 3T3-L1 adipocytes, indicating the potential role of PPARα in PC-mediated brown-like adipocyte formation. In conclusion, MFGM and milk PC induced adipose browning, which has major protective effects against obesity and metabolic dysfunction.

Li T ，Du M ，Wang H ，Mao X ... -  《-》

Resveratrol supplementation of high-fat diet-fed pregnant mice promotes brown and beige adipocyte development and prevents obesity in male offspring.

Maternal high-fat diet impairs brown adipocyte function and correlates with obesity in offspring. Maternal resveratrol administration recovers metabolic activity of offspring brown adipose tissue. Maternal resveratrol promotes beige adipocyte development in offspring white adipose tissue. Maternal resveratrol intervention protects offspring against high-fat diet-induced obesity. Promoting beige/brite adipogenesis and thermogenic activity is considered as a promising therapeutic approach to reduce obesity and metabolic syndrome. Maternal obesity impairs offspring brown adipocyte function and correlates with obesity in offspring. We previously found that dietary resveratrol (RES) induces beige adipocyte formation in adult mice. Here, we evaluated further the effect of resveratrol supplementation of pregnant mice on offspring thermogenesis and energy expenditure. Female C57BL/6 J mice were fed a control diet (CON) or a high-fat diet (HFD) with or without 0.2% (w/w) RES during pregnancy and lactation. Male offspring were weaned onto a HFD and maintained on this diet for 11 weeks. The offspring thermogenesis and related regulatory factors in adipose tissue were evaluated. At weaning, HFD offspring had lower thermogenesis in brown and white adipose tissues compared with CON offspring, which was recovered by maternal RES supplementation, along with the appearance of multilocular brown/beige adipocytes and elevated thermogenic gene expression. Adult offspring of RES-treated mothers showed increased energy expenditure and insulin sensitivity when on an obesogenic diet compared with HFD offspring. The elevated metabolic activity was correlated with enhanced brown adipose function and white adipose tissue browning in HFD+RES compared with HFD offspring. In conclusion, RES supplementation of HFD-fed dams during pregnancy and lactation promoted white adipose browning and thermogenesis in offspring at weaning accompanied by persistent beneficial effects in protecting against HFD-induced obesity and metabolic disorders.

Zou T ，Chen D ，Yang Q ，Wang B ，Zhu MJ ，Nathanielsz PW ，Du M ... -  《-》

Milk Polar Lipids Supplementation to Obese Rats During Pregnancy and Lactation Benefited Skeletal Outcomes of Male Offspring.

Dietary intervention to obese dams during pregnancy and lactation period provides avenues for improving metabolic profiles of the offspring. In the current study, the effects of polar lipids-enriched milk fat globule membrane (MFGM-PL) supplementation to obese dams during pregnancy and lactation on the skeletal outcomes of male offspring are investigated. MFGM-PL is supplemented to obese rats induced by high-fat diet during pregnancy and lactation at a dose of 400 mg kg-1 body weight. Results show that maternal MFGM-PL supplementation significantly ameliorates the stunted skeletal growth of male offspring at weaning. In adulthood offspring, maternal MFGM-PL supplementation protects against high-fat diet (HFD)-induced bone microstructure degeneration and bone marrow adipocyte accumulation. Further investigation shows that maternal supplementation of MFGM-PL significantly ameliorates insulin resistance and increases the mRNA expression of growth hormone releasing hormone (GHRH) in the hypothalamus of HFD offspring. The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis is subsequently enhanced in MFGM-PL + HFD offspring, contributing to the beneficial skeletal outcomes. The findings suggest that maternal MFGM-PL supplementation of HFD dam during pregnancy and lactation shows desirable effects on fetal skeletal development, with lasting beneficial programming impacts on skeletal outcomes of offspring.

Han L ，Du M ，Ren F ，Mao X ... -  《-》

Milk Fat Globule Membrane Attenuates High-Fat Diet-Induced Obesity by Inhibiting Adipogenesis and Increasing Uncoupling Protein 1 Expression in White Adipose Tissue of Mice.

Li T ，Gao J ，Du M ，Song J ，Mao X ... -  《Nutrients》