Obesity and weight loss differentially regulate autophagy in mouse ovarian granulosa cells.

OBJECTIVE: This study aimed to elucidate the impact of obesity and weight loss on autophagic processes in ovarian granulosa cells (GCs), given the crucial roles that these cells and this process play in oogenesis. METHODS: Three experimental groups were used: a control group (ND group), a high-fat diet-induced obese mouse model group (HFD group), and a swimming exercise group (SE group). Immunohistochemistry (IHC) and Western Blotting (WB) were used to detect protein expression in GCs. RESULTS: LC3B expression was higher in the HFD and SE groups than in the ND group (p<0.01), but lower in the SE group than in the HFD group (p<0.05). p62 expression was lower in the HFD and SE groups than in the ND group (p<0.01 and p<0.05, respectively), but higher in the SE group than in the HFD group (p<0.05). The LC3B-II/I ratio was elevated in the HFD group versus the ND and SE groups (p<0.05). p62 expression was lower in the HFD group than in the SE and ND groups (p<0.05 and p<0.01, respectively), and lower in the SE group than in the ND group (p<0.01). In IHC, the p-mTOR/mTOR ratio was lower in the HFD group than in the ND group (p<0.05), but higher in the SE group than in the ND and HFD groups (p<0.01). The AMPK/AMPK ratio was higher in the HFD group than in the ND group (p<0.01), but lower in the SE group than in the HFD group (p<0.01). In WB, the p-mTOR/mTOR ratio was lower in the HFD and SE groups than in the ND group (p<0.01), but higher in the SE group than in the HFD group (p<0.05). p-RPS6/RPS6 ratio was lower in the HFD group than in the ND group (p<0.01), but higher in the SE group than in both groups (p<0.01). CONCLUSIONS: Our findings suggest that obesity activates granulosa cell autophagy via AMPK/mTOR signaling, while weight loss partially restores homeostasis.