# Integrated Systemic and Adipose Depot-Specific Regulation of Adipogenesis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $416,961

## Abstract

PROJECT SUMMARY
A great deal of our understanding of the process of adipogenesis has come from in vitro studies on cultured
cell lines and adipose stromal fractions, focusing on the differentiation of committed preadipocytes into mature
lipid-laden adipocytes. These studies have provided a wealth of knowledge, including elucidating an elegant
cascade of mostly transcription factors that propels preadipocytes through the differentiation process into
mature adipocytes. However, there is still a large knowledge gap in our understanding of the integrated factors
that trigger this adipogenesis cascade in vivo and the influence of these pathways on the development of
obesity and metabolic disease. Our proposal is focused on addressing these knowledge gaps. We identified a
pathway in adipose tissue that is responsive to changes in diet and regulates endogenous adipocyte precursor
cell (APC) activity. We found that ADAMTS1 is a critical mediator of this pathway that gates a depot-specific
decision to induce adipogenesis in response to high-fat diet. We will test and define the function of this
pathway in physiological mechanisms that regulate the initiation of the differentiation program in APCs. Using
molecular and cellular approaches, as well as mouse models and samples from humans, we will elucidate the
roles, mechanisms and relevance to human physiology of the Adamts1 pathway in the in vivo regulation of
adipogenesis. In addition, we will reveal how this pathway modulates the systemic stimulus of high-fat diet to
generate context-specific responses in the adipose tissue during diet-induced obesity. These studies will
provide an integrated perspective on how this pathway functions to regulate adipogenesis and in the
pathogenesis of obesity and insights into the implications for metabolism.

## Key facts

- **NIH application ID:** 10163160
- **Project number:** 5R01DK114217-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Brian J Feldman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $416,961
- **Award type:** 5
- **Project period:** 2019-03-05 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163160

## Citation

> US National Institutes of Health, RePORTER application 10163160, Integrated Systemic and Adipose Depot-Specific Regulation of Adipogenesis (5R01DK114217-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10163160. Licensed CC0.

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