# Role of SIK3 in PKA/mTORC1 regulation of adipose browning

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $519,119

## Abstract

Project Summary: .
Obesity is at epidemic proportions in the US. Over 60% of the population is either overweight (Body Mass
Index [BMI] ≥25 to <30 kg/m2) or obese (BMI ≥30 kg/m2), placing them at risk for a large number of chronic
diseases, including insulin resistance, metabolic syndrome, and type 2 diabetes. The annual costs of obesity
exceed $100 billion, making it one of the most significant public health and economic issues facing the country.
Unfortunately, the treatment of obesity is unsatisfactory. Lifestyle and behavioral approaches have a modest,
and often transient, effect while FDA-approved therapeutic options targeting appetite or fat absorption have
poor tolerability and, in some cases, safety concerns. Thus, there is a critical need for novel approaches to
treat obesity. Agents acting via peripheral mechanisms to increase energy expenditure would be valuable. The
sympathetic nervous system (SNS) is well-known as an activator of brown adipose tissue (BAT) and the
“browning” of cells in white adipose tissue (WAT) depots to increase uncoupled mitochondrial respiration and
energy expenditure. Our earlier work established signaling cascades from β-adrenergic receptors (βARs) 
cAMP  protein kinase A (PKA)  p38 MAP kinase (MAPK), and also from PKA to mTORC1. These
downstream signaling modules are key to drive the transcription of brown adipocyte genes such as uncoupling
protein-1 (UCP1), PPAR-gamma coativator-1α (PGC-1α), and the broader program of mitochondrial
biogenesis. The Scientific Premise of this project is based upon our identification of substrates of PKA-
activated mTORC1 that convey the brown-adipose promoting machinery, and we will determine their molecular
mechanisms. Our long-term goal is to define signaling pathways that are critical to metabolic and
cardiovascular disease and, using this knowledge, to target pivotal components of these signaling pathways to
prevent or reverse the diseases.

## Key facts

- **NIH application ID:** 10922798
- **Project number:** 5R01DK132236-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** SHEILA COLLINS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $519,119
- **Award type:** 5
- **Project period:** 2023-09-06 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10922798

## Citation

> US National Institutes of Health, RePORTER application 10922798, Role of SIK3 in PKA/mTORC1 regulation of adipose browning (5R01DK132236-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10922798. Licensed CC0.

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