UC San Diego

Maternal obesity adversely affects offspring health through prenatal and postnatal metabolism, yet the mechanisms underlying these effects remain unknown. Adiponectin, an adipocyte-secreted hormone suppressed during obesity, may play a key role in understanding these outcomes. To investigate this, we studied the impact of maternal obesity on postnatal growth and the role of maternal adiponectin in these processes at postnatal day (P) 10 using C57BL/6 wild-type (WT) and adiponectin gene knockout (Adipoq-/-) mice fed a high fat (HF) diet. We found maternal HF feeding induced postnatal catch-up growth in offspring, signified by a greater body weight. This was attributed to an increased villi/crypt ratio in the small intestine (SI), which was associated with elevated intestinal proliferation and inflammation. Offspring from HF-fed Adipoq-/- dams exhibited similar rates of intestinal proliferation, more pronounced inflammation, and no change in body weight or villi/crypt ratio, suggesting adiponectin protects against maternal obesity-induced inflammation in offspring. Based on these findings, we studied nutrient supply and mammary gland (MG) development in these dams. Maternal HF feeding increased milk triglyceride (TG) levels in Adipoq-/- dams, potentially contributing to inflammation, while in WT dams, it increased milk extracellular vesicle (EV) size. WT dams on a HF diet exhibited a decreased percentage of alveolar epithelial tissue, suggesting impaired MG development, whereas Adipoq-/- dams on a chow diet exhibited reduced alveoli and increased adipose tissue, suggesting early involution. These findings indicate that adiponectin protects against maternal obesity-induced inflammation in offspring, influencing both nutrient supply and MG development.