SAT667 Follicle-Stimulating Hormone Does Not Directly Regulate Adipogenesis Via The FSH Receptor In Mice
Bibliographic record
Abstract
Abstract Disclosure: M. Loka: None. L. Ongaro Gambino: None. T. Uliasz: None. L.A. Jaffe: None. L. Kazak: None. D.J. Bernard: None. Rising rates of obesity are a serious public health challenge. Post-menopausal women are at higher risk of developing obesity and associated comorbidities than premenopausal women, with hormonal changes, such as reduced estrogens, likely to be contributing factors. Menopause is also characterized by increases in pituitary-derived follicle-stimulating hormone (FSH). Recent data suggest that FSH may directly stimulate adipogenesis and block thermogenesis in adipocytes. FSH reportedly decreased expression of thermogenic genes (Cox8b and Ucp1) in murine 3T3-L1 cells differentiated into adipocytes. FSH’s inhibitory effects were no longer apparent in the presence of an FSH-neutralizing antibody. The same FSH antibody reduced fat mass and increased lean mass in ovariectomized (OVX) female mice, a rodent model of menopause. In these studies, it was not established whether FSH acted directly through its canonical receptor (FSHR) in adipocytes to mediate its effects. To address this gap, we differentiated 3T3-L1 cells to adipocytes and treated with FSH. In contrast to the earlier report, FSH did not alter the expression of markers of lipogenesis (Cebpa and Pparg2) or thermogenesis (Cox8b and Ucp1) nor did it impact mitochondrial respiration or lipid accumulation. We also did not detect Fshr mRNA in these cells. We next differentiated the stromal vascular fraction from inguinal adipose tissue of adult male mice into white adipocytes. After 10 days of differentiation, FSH treatment did not alter expression of several markers of adipogenesis and did not affect lipid accumulation. To assess FSH actions in vivo, we generated adipocyte-specific Fshr knockout mice (Fshrfx/fx;Adipoq-Cre, hereafter cKO). Ten-week-old cKO and control female mice were OVX and maintained on standard chow. Eight to 10 weeks later, we performed glucose tolerance and insulin tolerance tests, and determined body composition by EchoMRI. Cre-mediated recombination of the floxed Fshr locus in adipocytes was successful, but did not alter body weight, fat or lean mass, or glucose metabolism in cKO relative to control OVX mice. Furthermore, using a newly developed FSHR-3xHA knockin mouse model, we detected FSHR protein expression in ovary, but not in inguinal and perigonadal white adipose depots or in intrascapular brown adipose tissue. We similarly failed to detect Fshr mRNA in various fat depots in control mice. Collectively, our results fail to show FSH effects on adipogenesis in vitro and challenge the hypothesis that FSH acts through the classical FSHR in adipocytes in vivo. Presentation: Saturday, June 17, 2023
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.010 | 0.003 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".