Adipose Tissue‚ Appetite‚ and Obesity

ORF51-04 - Tanycytic TSHR and IGF-1R Regulate Ingestive Behavior, Blood-Hypothalamus Barrier Plasticity, and Adipose Remodeling

Monday, June 15, 2026

2:00 PM - 2:15 PM CT

Location: Room W181AB

Oral Abstract Presenter(s)

ZT

Zehra Tumoglu, M.D.

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, NY, New York, United States

Co-Author(s)

AG

Anisa Gumerova, MD, PhD (she/her/hers)

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, NY, New York, United States
GP

Georgii Pevnev, MD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
EW

Emily Weiss, MS (she/her/hers)

Mount Sinai
New York, NY, New York, United States
OM

Ofer Moldavski, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, NY, New York, United States
SS

Steven Sims, MS (he/him/his)

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
MM

Maryam Mansoori, PhD (she/her/hers)

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
New York, NY, New York, United States
RL

Rauf Latif, PhD

Associate Professor
Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, New York, United States
GB

Guzel Burganova, MD PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
SP

Surabhi Parte, BS (she/her/hers)

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, New York, United States
RP

Rukmani Pandey, PhD (she/her/hers)

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, New York, United States
OB

Orly Barak, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
TF

Tal Frolinger, PhD (she/her/hers)

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, NY, New York, United States
TY

Tony Yuen, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
KG

Ki Goosens, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, NY, New York, United States

Senior Author/Primary Investigator(s)

TS

Terry J. Smith, MD

Department of Ophthalmology and Visual Sciences and Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
Ann Arbor, United States
MZ

Mone Zaidi, MD, PhD (he/him/his)

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, NY, New York, United States

The traditional view that the thyroid-stimulating hormone (TSH) exerts its actions solely on its primary endocrine target, the thyroid gland, has been increasingly challenged. Recently, utilizing RNAscope in situ hybridization, we documented, for the first time, Tshr single-transcript level expression in over 173 brain nuclei, sub-nuclei and regions, with prominent enrichment in hypothalamic tanycytes. The latter glial cells are known to convey metabolic signals across the blood-hypothalamus barrier (BHB) and regulate energy balance. In gain-of-function studies, intracerebroventricular (ICV) infusions of a highly specific TSHR agonist, MS438, profoundly increased BHB permeability in fasted mice, resulting in significant increases in peanut butter consumption. This was associated with greater loss of body adiposity, as well as increased influx of fatty acids across the BHB, increased NPY expression (as a measure of increased appetite), and increased secretion of ghrelin from the stomach fundus. Conversely, in loss-of-function studies, haploinsufficient Tshr+/– mice displayed decreased BHB permeability and were protected from body weight loss in response to short-term fasting. Additionally, tanycyte specific AAV—CRISPR—Tshr knockout in WT mice via ICV microinjections resulted in significant decreases in peanut butter consumption. Evidence has emerged that insulin-like growth factor 1 receptor (IGF-1R) and TSH receptor (TSHR) colocalize to the perinuclear and cytoplasmic compartments in fibroblasts and thyrocytes. Our RNAscope analysis revealed that ~40% of TSHRs were colocalized with IGF-1Rs in α1, α2, β1 and β2 tanycytes, suggesting a conserved intracellular organization of TSHR—IGF-1R signaling across diverse cell types. To study whether tanycytic TSHR and IGF-1R interaction affects ingestive behavior, four groups of haploinsufficient Tshr+/– mice were ICV-cannulated and received vehicle, TSH (8 µg), 1H7 monoclonal blocking antibody that targets the α-subunit of IGF-1R (8 µg) and a cocktail of TSH + 1H7 (each 8 µg) ICV, respectively. All mice had free access to peanut butter, and consumption was quantified at 30- and 60-minutes following food exposure. In line with our MS438 studies, ICV microinfusions of TSH markedly increased peanut butter intake at both time points compared to that of vehicle-infused mice. Surprisingly, in the TSH + 1H7 group, 1H7 microinfusion blocked TSH-induced phosphorylated ERK immunoreactivity in α2 tanycytes, and abolished TSH-induced increase in peanut butter consumption. Collectively, our findings establish a new role for tanycytic TSHRs in regulating BHB plasticity, ingestive behavior and adipose tissue remodeling. In addition, we provide novel neuroanatomical and functional evidence supporting tanycytic-specific TSHR—IGF-1 crosstalk in the regulation of ingestive behavior.