SAT-657 - Menopausal Estrogen Deficiency and Dietary Fatty Acids Regulate Adipocyte Function and Fatty Acid Uptake in Engineered Adipose Tissue

Obesity, defined as the excessive accumulation of adipose tissue, affects 890 million people worldwide. Among American women, obesity prevalence rises markedly from 65% to 73.8% after age 60­, a pattern that coincides with the menopausal transition. During the premenopausal period, the ovaries are the primary site of estradiol (E2) synthesis. As ovarian function declines with menopause, the body shifts toward estrone production in adipose tissue. This reduction in circulating E2 has been established as a key driver of postmenopausal obesity, as low E2 promotes adipocyte hypertrophy and chronic low-grade inflammation. Concurrently, increases in obesity rates have been linked to low socioeconomic status, where malnutrition and poor diet are common, implicating dietary fatty acid composition as a modifiable risk factor.

Adipose tissue regulates energy balance through lipogenesis, the esterification of dietary fatty acids into triglycerides (TAGs), and lipolysis, the hydrolysis of TAGs into free fatty acids. Saturated fatty acids (SFAs), such as palmitic acid, constitute 12-15% of total nutrient intake and induce adipose inflammation, a hallmark of obesity. In contrast, monounsaturated fatty acids (MUFAs), most prominently oleic acid, are associated with elevated lipolytic activity, promoting favorable metabolic states. Despite substantial literature characterizing the independent effects of E2 and dietary fatty acids on adipocyte function, their combined influence remains poorly understood.

This study investigates how low E2 levels, as observed in postmenopausal women, interacts with dietary fatty acids to modulate adipocyte metabolism and contribute to obesity. To address this, we developed a physiologically relevant in vitro model by encapsulating adipocytes within three-dimensional collagen hydrogels, which preserve cell-cell and cell-extracellular matrix interactions absent in conventional two-dimensional culture systems. Preliminary findings indicate that low E2 combined with oleic acid reduces fatty acid uptake and enhances lipolysis, consistent with a healthier adipocyte phenotype. Conversely, palmitic acid treatment under low E2 conditions decreased triglyceride storage and lipid desaturation, suggesting intracellular accumulation of SFAs and potential lipotoxicity. Palmitic acid further elevated inflammatory markers and indicated possible leptin resistance, a state associated with hyperphagia and unhealthy adipocytes. Ongoing work includes confocal imaging to visually assess adipocyte morphology and pathway inhibition using sulfosuccinimidyl oleate (SSO) to validate the fatty acid uptake mechanism under investigation. These findings will ultimately inform dietary recommendations for postmenopausal women and advance understanding of hormonal regulation of adipose tissue metabolism.

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