Jarom Morris
Effect of Obesity vs Diet on the Secretome of Adipocytes
Mentor: Keren Hilgendorf, PHD
Department: Biochemistry
Background: Dr. Hilgendorf’s lab investigates how adipocytes from different metabolic states influence breast cancer cell growth. Previous research shows that lean inguinal adipocytes inhibit breast cancer growth, whereas adipocytes from obese or visceral fat depots do not. The lean inguinal adipocyte secretome induces ferroptosis in cancer cells without affecting normal epithelial cells, with 9S-HODE identified as a key inhibitory component.
Methods: To explore whether differences in 9S-HODE secretion between lean and obese adipocytes are due to diet or obesity-related transcriptional changes, we used four mouse models: ob/ob mice (leptin gene knockout) on a normal chow diet, calorie-restricted mice on a high-fat diet, mice on a normal chow diet, and mice on a high-fat diet. Adipocytes were isolated, and their secretomes were collected and used to culture breast cancer cell lines. Cell growth was monitored with an IncuCyte system.
Results: The secretome from calorie-restricted mice on a high-fat diet showed no inhibition of cancer cell growth, similar to that from adipocytes on a high-fat diet. In contrast, the secretome from OBOB mice inhibited cancer cell growth similarly to lean inguinal adipocytes from mice on a normal chow diet.
Conclusions: Our findings suggest that dietary factors, rather than obesity itself, significantly influence 9S-HODE secretion. The ability of adipocytes to inhibit cancer cell growth is modulated by diet, as shown by effects of secretomes from calorie-restricted high-fat diet mice and high-fat diet adipocytes compared to inhibitory effects of secretomes from OBOB mice and lean inguinal adipocytes on normal chow diet.