# CTRP and Metabolic Control

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $625,807

## Abstract

Project Summary
Hepatic lipid synthesis and catabolism is tightly regulated. Altered lipogenesis, lipid utilization, and lipoprotein
secretion in liver can adversely affect local and systemic lipid homeostasis. While the critical role of insulin in
promoting hepatic lipid and lipoprotein synthesis is widely studied, major knowledge gaps exist regarding
hormones that suppress hepatic lipogenesis and promote fat oxidation. Since our initial discovery of the
CTRP family of secreted hormones, we have systematically characterized the metabolic function and
mechanisms of action of each CTRP using gain- and loss-of-function mouse models. In this competitive
renewal application, we propose focused studies of CTRP1, based on our recent discovery that this hormone
plays a critical role in regulating hepatic lipid metabolism. Adipose and liver are the two major tissues that
express CTRP1. Even on a control low-fat diet (LFD), aged CTRP1 knockout (KO) mice have strikingly
enlarged liver, pronounced hepatic steatosis, and fibrosis. When obesity is induced with a high-fat diet
(HFD), Ctrp1-KO mice develop a significantly more severe non-alcoholic fatty liver disease (NAFLD) and this
is associated with a deficit in mitochondrial β-oxidation. When challenged with a non-alcoholic steatohepatitis
(NASH)-provoking diet, Ctrp1-KO mice have markedly more severe phenotypes. In contrast to the loss-of-
function phenotypes, overexpression of CTRP1 in primary mouse hepatocytes suppresses lipid synthesis
and promotes fat oxidation and mitochondrial respiration. Collectively, these data indicate that liver is a major
target tissue of CTRP1; disrupting CTRP1-regulated pathways in liver affects hepatic lipid metabolism,
inflammation, and fibrosis. We propose two specific aims toward understanding the contribution of CTRP1 to
hepatic lipid metabolism (Aim 1) and the protective mechanisms of CTRP1 in mitigating the severity of fatty
liver, inflammation, and fibrosis in the context of NASH (Aim 2). The completion of these aims will provide
major advancement and critical insights into novel pathways regulating hepatic lipid metabolism by the
secreted hormone, CTRP1. This knowledge may inform innovative strategies to mitigate NAFLD and NASH
in clinical settings.

## Key facts

- **NIH application ID:** 10980173
- **Project number:** 2R01DK084171-13
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Guang William Wong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $625,807
- **Award type:** 2
- **Project period:** 2010-07-15 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980173

## Citation

> US National Institutes of Health, RePORTER application 10980173, CTRP and Metabolic Control (2R01DK084171-13). Retrieved via AI Analytics 2026-07-30 from https://api.ai-analytics.org/grant/nih/10980173. Licensed CC0.

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