# ApoJ as a novel hepatokine targeting muscle glucose metabolism

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $432,500

## Abstract

A major challenge in the field of metabolic physiology has been to understand the interorgan
communication networks linking to glucose metabolism. One critical factor for this interorgan system is
now known as hepatokines, identified from liver-derived proteins, and that play a pivotal role in
regulating glucose metabolism and insulin sensitivity in skeletal muscle. ApoJ (apolipoprotienJ, also
called clusterin) was not previously suspected to be involved in the regulation of glucose homeostasis
and insulin signaling. Our preliminary data demonstrate that ApoJ may function as a hepatokine
targeting insulin signaling and glucose metabolism in skeletal muscle, which could be mediated via the
LRP1/2 (low-density lipoprotein receptor-related protein-1/2) signaling cascade. We thus hypothesize
that the ApoJ → LRP1/2 axis is a novel metabolic signaling network that is crucial for the maintenance
of normal glucose homeostasis and insulin signaling and that this couples with the insulin receptor
system. The overall objective of this proposal is to identify ApoJ as a novel hepatokine that controls
muscle glucose homeostasis via LRP1/2 signaling coupled with the insulin receptor system.
Specifically, Aim1 will establish the biological function of ApoJ as a new hepatokine in glucose
metabolism. Aim2 will determine whether the ApoJ → LRP1/2 signaling pathway is a key component of
insulin action in skeletal muscle. Aim3 will elucidate the cellular mechanisms for the insulin-sensitizing
effects of ApoJ. To accomplish these aims, we will use state-of-the-art technologies, including a
conditional floxed ApoJ, LRP1 and LRP2 models as well as human subjects to clarify the metabolic
function of the ApoJ → LRP2 axis in the context of interorgan communication networks. These studies
provide a unique opportunity to establish a new paradigm in which the ApoJ → LRP2 signaling network
is a key determinant of glucose homeostasis, and may offer a novel target for the treatment of obesity
and diabetes.

## Key facts

- **NIH application ID:** 9978058
- **Project number:** 5R01DK111529-05
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** YOUNG-BUM KIM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $432,500
- **Award type:** 5
- **Project period:** 2016-09-20 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978058

## Citation

> US National Institutes of Health, RePORTER application 9978058, ApoJ as a novel hepatokine targeting muscle glucose metabolism (5R01DK111529-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9978058. Licensed CC0.

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