# Mechanisms of human adipose depot development and impact of Diabetes

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2022 · $494,125

## Abstract

ABSTRACT
More than total adiposity, the relative distribution of adipose tissue among central and peripheral depots is
a critical determinant of Type 2 Diabetes (T2DM) and cardio metabolic disease risk. The goal of this
proposal is to use novel mesenchymal progenitor cell derivation and single-cell clone genomic sequencing
approaches to fully identify and characterize the diversity of adipocytes that compose these human depots and
their developmental mechanisms. To this end, we will leverage exciting recent methods whereby we can
generate large numbers of mesenchymal progenitor cells from human adipose tissue with minimal loss of
multipotency. These cells differentiate into adipocytes that are similar to those from the depot of origin, and
their transcriptomes reveal the existence of at least three types of “white” human adipocytes, as well as the
thermogenic “beige/brite” type. We are now in a strong position to test the hypothesis that metabolically
distinct human adipose depots, gluteal and abdominal, are composed of different adipocyte classes that
develop from specific mesenchymal progenitor cells, and to provide full transcriptomic profiles of these
adipocytes and their progenitors. Furthermore, it is known that diabetes affects multipotent progenitor cells,
leading to impaired capacity to generate healthy adipocytes and repair tissue, further deterioration of insulin
responsiveness. We will test the hypothesis that human T2DM alters mesenchymal progenitor diversity
and determine how this defect leads to abnormal adipose tissue development in vivo. Our specific aims are:
1. To test the hypothesis that the different functional properties of human adipose tissue depots are due to
intrinsic differences in their content of adipocyte subtypes derived from specific mesenchymal progenitor
cells. 2: To test the hypothesis that T2DM preferentially impairs development of specific mesenchymal
progenitor subsets and adipocytes derived from these cells, and 3: To define the physiological properties of
adipocyte subtypes through tissue generation in vivo. These studies will provide a new high-resolution view
of the cellular structure of human adipose tissue depots, of developmental mechanisms that lead to adipocyte
subtypes, and insight into developmental alterations that contribute to T2DM physiopathology.

## Key facts

- **NIH application ID:** 10418655
- **Project number:** 5R01DK123028-04
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Silvia Corvera
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $494,125
- **Award type:** 5
- **Project period:** 2019-09-17 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10418655

## Citation

> US National Institutes of Health, RePORTER application 10418655, Mechanisms of human adipose depot development and impact of Diabetes (5R01DK123028-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10418655. Licensed CC0.

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