# The Lipidomics of Adipose Tissue Thermogenesis

> **NIH NIH K01** · JOSLIN DIABETES CENTER · 2020 · $142,856

## Abstract

Project Summary/Abstract
Obesity is a global pandemic with enormous financial burden and health cost due both to the increasingly large
proportion of the population who are overweight or obese and the broad range of associated sequelae such as
cardiovascular disease, type 2 diabetes, and some cancers. The development of strategies to prevent or treat
human obesity is therefore extremely important. Recently, a great deal of interest has been centered on the
metabolic capacity of brown fat in humans and the discovery and standardization of treatment regiments that
activate brown fat thermogenesis and expend energy. In order to activate brown adipose tissue, several
research strategies have been pursued, including both pharmacological interventions and physiologic cold
exposure. Unfortunately, the thermogenic effect of many compounds that occurs in mice is not observed in
humans, although recently B-3 adrenergic agonists that activate human BAT have been recently been
reported. To this end, an innovative approach is proposed wherein I plan to investigate bioactive lipids as a
novel class of circulating factors with potential pro-thermogenic effects in brown adipose tissue. Recently,
studies have demonstrated that lipid molecules can act as hormones secreted to act as signaling molecules in
distal organs. These lipids promote insulin sensitivity and glucose tolerance through their interaction with
proteins located on the cell membrane. Conventionally, lipids have not been considered as potential endocrine
factors. With this in mind, I have investigated the potential of lipids to act as secreted molecules that mediate,
at least in part, the physiologic response to cold challenge. Preliminary studies have made the novel discovery
that the lipid one specific target lipid species increases in circulation of mice and humans that are exposed to
cold and further, systemic injection of this lipid can increase thermogenesis. This approach is innovative
because lipid molecules have not been previously reported as secreted mediators of thermogenesis. In this
proposal, I will systematically determine the effect of this lipid on whole body energy metabolism and determine
the underlying molecular mechanisms that mediate enhanced thermogenesis after treatment with our target
lipid. These results could a have significant impact in the development of treatments for obesity and
cardiovascular disease.

## Key facts

- **NIH application ID:** 9964799
- **Project number:** 5K01DK111714-04
- **Recipient organization:** JOSLIN DIABETES CENTER
- **Principal Investigator:** MATTHEW D LYNES
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $142,856
- **Award type:** 5
- **Project period:** 2017-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964799

## Citation

> US National Institutes of Health, RePORTER application 9964799, The Lipidomics of Adipose Tissue Thermogenesis (5K01DK111714-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9964799. Licensed CC0.

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