# EMC10, a novel obesity-regulated circulating factor, regulates energy and metabolic homeostasis

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $359,775

## Abstract

PROJECT SUMMARY
 Obesity, an epidemic affecting more than one third of the US population, is a major risk factor for metabolic
disorders including type 2 diabetes and cardiovascular disease. Protein secreted from metabolic organs
including adipokines, myokines, hepatokines and cardiokines are known to play important roles in inter-organs
communication leading to fine-tuning and maintenance of glucose and energy homeostasis in the body. In
addition, many of these secreted proteins have been shown to be excellent biomarkers for the diagnosis of
metabolic dysfunction and can be potential therapeutic targets. In a screen to identify differentially regulated
genes in adipose tissue during obesity, we observed that the expression of a secreted endoplasmic reticulum
(ER)-associated protein, Emc10 (also known as Inm02, hHss1 and Mirta22), is specifically downregulated in
the subcutaneous fat in obese mice and human. Consistent with a decreased in Emc10 expression in adipose
tissues, circulating levels of Emc10 are also downregulated in obese mice. To investigate the role of Emc10 on
metabolic homeostasis, we generated Emc10 global knockout (KO) mouse. Surprisingly, in our preliminary
studies, we observed that disruption of Emc10 in mice results in protection from diet-induced obesity and
metabolic dysfunction. Further, we revealed that obesity resistance phenotype observed in Emc10 KO is
contributed by increase in oxygen consumption and simultaneous modulation of lipolysis and lipogenesis after
HFD feeding. In this proposal, we will determine the role of Emc10 on energy metabolism with three specific
aims. In Aim 1, we will determine the physiological impact of Emc10 KO on energy and metabolic homeostasis
in both male and female animals by subjecting them to dietary treatment. In addition we will determine the
cellular processes regulated by Emc10 ablation and whether the KO mice are more susceptible to browning
induction. In Aim 2, we will determine the role of circulating Emc10. Confirmation of extracellular role of Emc10
on energy homeostasis would facilitate the use of Emc10 as potential therapeutic targets. We will also
determine whether downregulation of Emc10 in mice fed HFD is a compensatory response to counteract
obesity and finally, we will find out whether ablation of Emc10 in obese mice would prevent further weight gain
and perhaps promote weight loss. In Aim 3, we will examine whether AMPK and CREB signaling pathways are
involved the regulation of Emc10 on energy metabolism. Results from our proposed experiments will likely
provide insights on regulatory mechanisms of Emc10 on energy and metabolic homeostasis and likely to
reveal approaches for novel therapeutic strategy.

## Key facts

- **NIH application ID:** 9917766
- **Project number:** 5R01DK109015-05
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Chong Wee Liew
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $359,775
- **Award type:** 5
- **Project period:** 2016-07-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9917766

## Citation

> US National Institutes of Health, RePORTER application 9917766, EMC10, a novel obesity-regulated circulating factor, regulates energy and metabolic homeostasis (5R01DK109015-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9917766. Licensed CC0.

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