# Regulators of adipocyte oxidative metabolism

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $24,767

## Abstract

PROJECT SUMMARY
Adipose oxidative metabolism is central to human health. Defects in adipocyte mitochondria are linked to
adipocyte dysfunction and insulin resistance, whereas lifestyle interventions and pharmacological agents
that promote adipocyte oxidative capacity promote metabolic health and insulin sensitivity. Studies over
several years have identified important regulators of adipocyte oxidative metabolism, such as members
of the PGC-1 coactivator family, and nuclear receptors of the PPAR (peroxisome proliferator-activated
receptor) and ERR (Estrogen-related receptor) subfamilies. These transcription factors exert their effects
on gene expression and cellular function by both direct and indirect regulation of hundreds of genes that
coordinately promote mitochondrial biogenesis and oxidative metabolism. Mining of genes regulated by
PGC-1s and ERRs, coupled to bioinformatic approaches to determine associations of PGC-1/ERR
targets with PPAR pathways and metabolism, has led us to identify a new and poorly characterized
protein, Mcrip2, as highly associated with adipocyte oxidative metabolism. The premise of this proposal
is that Mcrip2, a protein of unknown cellular and molecular function, that has not been linked yet to
metabolism or physiology, is induced by PGC-1, PPAR and ERR factors, acts to enhance basal and
adrenergically stimulated expression of oxidative metabolism genes, and is thus a critical element of the
regulatory networks that control adipocyte oxidative metabolism. Interactions of Mcrip2 with proteins
involved in mRNA processing and turnover suggest that Mcrip2 exerts its function by regulating gene
expression at the post-transcriptional level. Notably, we know little about mechanisms controlling post-
transcriptional steps in adipocyte oxidative metabolism pathways. The proposed work will define the role
of Mcrip2 in adipocyte basal oxidative metabolism and adrenergic responses, using gain- and loss-of
function approaches in primary brown and inguinal adipocytes, and delineate the level at which Mcrip2
impacts gene expression. It will also determine the physiologic significance of Mcrip2 for mitochondrial
function and adaptive thermogenesis, using a mouse model. Finally, the studies will elucidate the
mechanism by which Mcrip2 impacts adipocyte biology, by defining Mcrip2 protein domains required for
function and critical Mcrip2 interacting partners in basal and adrenergically stimulated adipocytes. In
sum, the work will give first insights into post-transcriptional regulation of adipocyte oxidative function,
and may suggest new targets and avenues for therapeutic intervention in diseases that can benefit from
increases in oxidative capacity, such as obesity and obesity-related diseases.

## Key facts

- **NIH application ID:** 10632187
- **Project number:** 3R01DK128933-01A1S1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Anastasia Kralli
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $24,767
- **Award type:** 3
- **Project period:** 2022-08-12 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10632187

## Citation

> US National Institutes of Health, RePORTER application 10632187, Regulators of adipocyte oxidative metabolism (3R01DK128933-01A1S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10632187. Licensed CC0.

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