# Roles of Sphingosine Kinase 1 in adipocyte thermogenesis

> **NIH NIH F31** · VIRGINIA COMMONWEALTH UNIVERSITY · 2021 · $41,603

## Abstract

Project Summary
 Obesity is a health crisis in America that affects both adults and children and leads to many adverse
health outcomes. Therefore, novel approaches to treating obesity are of intense interest. Brown and beige
adipose tissue has been the focus of many recent obesity-related studies. Brown and beige adipocytes have a
high mitochondria content, and fatty acid oxidation is enhanced. Furthermore, because these tissues express
Uncoupling Protein 1 (UCP1), a significant portion of energy from fatty acid metabolism is lost from heat. While
the existence of brown adipose in humans is controversial, recent studies have focused on the process by which
white adipocytes convert to beige, thermogenic adipocytes, because if this process could be deliberately
regulated it would result in decreased adipose tissue and hence constitute a potential treatment for obesity.
 This proposal aims to shed light on a novel function of Sphingosine Kinase 1. β₃ adrenergic receptor
stimulation promotes conversion of white adipocytes to beige (“beiging”). My preliminary data show that in vivo
stimulation of β₃ adrenergic receptor with CL 316243 (CL) increases Ucp1 and SphK1 mRNA. Even further,
these results were recapitulated in vitro where β₃ adrenergic receptor stimulation of white WT adipocytes showed
increased SphK1 and Ucp1 mRNA expression, which was attenuated in SphK1-deficient white adipocytes.
Additionally, SphK1 null adipocytes were unable to induce PGC1α and PGC1β, both of which are co-activators
of transcription factors for UCP1, the driver for thermogenesis. Based on these preliminary data, I hypothesize
that SphK1 mediates beiging of white adipocytes resulting in mitochondrial uncoupling, leading to adipose tissue
thermogenesis. This project is divided into two aims to accomplish this goal. Aim 1 will investigate the role of
SphK1 in adipocyte beiging in vivo and in vitro, and aim 2 will elucidate the mechanism(s) by which SphK1
regulates beiging in adipocytes.
 The experiments proposed here will establish the importance of SphK1 in the conversion of white
adipocytes to beige and its role in thermogenesis in vivo. Additionally, this proposal will determine the pathway
via which SphK1 signals to control adipocyte thermogenesis. Therefore, my study will reveal a new link between
SphK1 signaling and adipocyte thermogenesis, which may then serve as a potential novel therapeutic target to
reduce obesity.

## Key facts

- **NIH application ID:** 10315416
- **Project number:** 1F31DK129028-01A1
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Yolander Valentine
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $41,603
- **Award type:** 1
- **Project period:** 2021-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10315416

## Citation

> US National Institutes of Health, RePORTER application 10315416, Roles of Sphingosine Kinase 1 in adipocyte thermogenesis (1F31DK129028-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10315416. Licensed CC0.

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