Neuroendocrinology and Pituitary

SUN-031 - Long-Term Diet-Induced Obesity in Mice Is Associated with Hypothyroidism and Female-Biased Somatotrope Dysfunction.

Sunday, June 14, 2026

9:00 AM - 4:00 PM CT

Location: ENDOExpo; Poster Floor

Abstract Poster Presenter(s)

Tiffany Miles, PhD

Instructor
Arkansas Children's Hospital/Arkansas Children's Nutrition Center
Little Rock, AR, United States

Co-Author(s)

AO

Angela Odle, Ph.D.

Assistant Professor
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
NA

Noor Akhter, Ph.D.

Associate Professor
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
MS

Mohsin Syed, Ph.D.

Associate Professor
University of Arkansas
Little Rock, Arkansas, United States
AH

Ashley K. Herdman, Ph.D. (she/her/hers)

Graduate Assistant
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
AL

Alex Lagasse, n/a

University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
AH

Anessa Haney, B.A.

Reearch Asociate
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
CB

Cole Bolen, n/a (he/him/his)

University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States

Senior Author/Primary Investigator(s)

AM

Angus MacNicol, Ph.D.

University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
GC

Gwen V. Childs, Ph.D. (she/her/hers)

Distinguished Professor
University of AR Medical Sci/College of Medical
Little Rock, Arkansas, United States
MM

Melanie C. MacNicol, Ph.D.

Associate Professor
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States

Long-term obesity increases the risk of hypothyroidism coupled with reduced pituitary somatotropic function and a decline in serum growth hormone (GH) levels. The molecular mechanisms underlying the pituitary response to obesity are not fully understood. Our recently reported single-cell RNA-sequencing study (scRNA-seq) compared pituitary cells from male and female FVB-NJ-P129 mice after a short-term (10-15 weeks) 60% high-fat diet (HFD) under thermoneutral conditions for mice (29-32C). Pituitary cells in females showed evidence of oxidative stress in response to the short-term HFD, whereas male pituitary cells appeared more resilient. Both sexes showed weight gains greater than 20 g and increased serum thyroid-stimulating hormone (TSH) levels, but only females exhibited significantly decreased serum GH pulses. We have extended these studies to assess the impact of long-term obesity upon the pituitary in mice exposed to the HFD for 42 wks, also under thermoneutral conditions. Both sexes showed elevated levels of serum leptin and inflammatory markers, and maintained weight gains exceeding 30 g for over 20 weeks. They also showed significantly lower activity in metabolic cages. Increased serum TSH levels indicating hypothyroidism were supported by a 2.24-fold decline in serum thyroxine (T4) levels in females and a similar trend (1.7-fold decline) in males (not significant). However, only the obese females showed significantly reduced (61%) serum GH levels. Analysis of pituitary single-cell transcriptomics in both sexes revealed reduced cell numbers (30-47%) in somatotrope and thyrotrope clusters identified following scRNA-seq. Despite these reductions in cell number, Ingenuity Pathway Analysis (IPA) of genes differentially expressed (DEGs) by these clusters revealed active canonical pathways related to growth factor induction, enhanced protein synthesis, and MAPK/ERK signaling, suggesting the cells were being stimulated. In contrast, however, females showed a second somatotrope cluster—absent in males—that was also reduced by 25% following the HFD and expressed DEGs representing CREB and Protein Kinase A pathways that were downregulated, consistent with decreased somatotrope function. Reduced serum GH in females also correlated with decreased Gh mRNA expression in pituitary multihormonal and stem cell clusters. The rise in serum TSH was associated with a 3X increase in Tshb mRNA levels in the pituitary stem/progenitor cell population, which is consistent with stimulation of thyrotropes as a result of reduced thyroid hormone negative feedback. These studies reveal sex differences in response to the obese state. Additionally, two populations of somatotropes were detected in females, both showing different degrees of increased vulnerability to the obese state, possibly as a consequence of a more rapidly developed hypothyroid condition.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*