# Developmental genes, miRNAs and adipose tissue

> **NIH NIH R01** · JOSLIN DIABETES CENTER · 2022 · $625,298

## Abstract

Project Abstract/Summary
 This is a competitive renewal of NIH grant DK082659 entitled “Developmental Genes, miRNAs and
Adipose Tissue”. Obesity is increasing at epidemic proportions and is a major driving force in the pathogenesis
of type 2 diabetes and metabolic syndrome. Over the past decade it has become clear that both white and
brown fat are heterogeneous. Thus, accumulation of visceral WAT is associated with insulin resistance and
increased risk of metabolic disease, whereas accumulation of subcutaneous WAT may even be protective.
This is due, at least in part, to intrinsic, i.e., cell-autonomous, functional differences between adipocytes in
these depots. Indeed, recent studies by us and others have shown that there is genetic and functional
heterogeneity of white adipocytes within a single depot. Using bioinformatics approaches and single cell
cloning, we have now identified lineage tracing markers for at least three classes of white adipocytes in
addition to those above. We have also found that different adipose depots differ in their expression of miRNAs
and that there are alterations in miRNAs and miRNA processing in adipose tissue in obesity and aging.
Furthermore, fat-specific knockout of the miRNA processing enzyme Dicer alters WAT and BAT development,
systemic glucose and lipid metabolism, and response to stress. In exciting recent data, we have shown that
adipose tissue is a major source of circulating exosomal miRNAs and that these can regulate gene expression
in other tissues, forming a novel mode of adipose communication with other tissues. These data have led to
two inter-related hypotheses. First, we hypothesize that - in addition to classification of adipose tissue into
white, brown and beige fat - white adipocytes themselves are heterogeneous in nature and that this
heterogeneity programs differences in mRNA expression and adipocyte function. Secondly, these different
classes of white and brown adipocytes differ in their miRNA expression and that a subset of these miRNAs is
released in exosomes into the circulation where they act as novel regulators of the effects of fat in other
tissues. The specific aims for the next grant period are to: 1) Complete the characterization of white adipocyte
heterogeneity using the newly identified lineage markers and expand this using single cell RNAseq to define
different subtypes of preadipocyte/adipocytes which differ in function and role in metabolic regulation. 2)
Continue to explore the role of adipose tissue derived circulating exosomal miRNAs in metabolism by
identifying the molecular signature governing adipocyte miRNA exosomal secretion in vitro and developing an
in vivo method for identification of fat- and other tissue-derived circulating exosomal miRNAs. We will also
assess exosomal miRNAs in serum of humans with lipodystrophy and obesity and assess the ability of
exosomal miRNAs to regulate gene expression in other tissues. Together these data will deepen our
understanding of ...

## Key facts

- **NIH application ID:** 10371056
- **Project number:** 5R01DK082659-14
- **Recipient organization:** JOSLIN DIABETES CENTER
- **Principal Investigator:** C RONALD KAHN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $625,298
- **Award type:** 5
- **Project period:** 2009-03-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10371056

## Citation

> US National Institutes of Health, RePORTER application 10371056, Developmental genes, miRNAs and adipose tissue (5R01DK082659-14). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10371056. Licensed CC0.

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