# Lipid metabolism and adipose tissue function

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2024 · $484,709

## Abstract

Project Summary
The prevalence of obesity has increased worldwide to epidemic proportions. Dysfunctional white adipose
tissue (WAT) and brown adipose tissue (BAT) have been implicated in the pathogenesis of obesity and its
related metabolic syndrome. BAT is densely packed with mitochondria and requires fatty acid (FA) oxidation to
support thermogenesis. In comparison, WAT serves as a main energy storage organ and the FA oxidation in
WAT is relatively low at ambient temperature. Chronic cold exposure induces browning of subcutaneous WAT
to become thermogenic beige AT with increased FA oxidation capacity. Although FA oxidation is known to be a
critical and fundamental metabolic end point in both humans and rodents, it is not completely clear how
adipocyte FA oxidation is regulated post-translationally and how it contributes to whole-body energy
metabolism in an autonomous manner. In this regard, our preliminary studies provide compelling evidence that
a protein encoded by Apolipoprotein 6 (ApoL6) is a selective regulator of mitochondrial trifunctional protein
(TFP), the key enzyme catalyzing FA β-oxidation. ApoL6 is highly expressed in WAT and differentiated
adipocytes. In contrast, BAT normally expresses low levels of ApoL6, which increases during obesity or
thermoneutrality-induced whitening. We found that in the basal condition, ApoL6 is localized to mitochondria,
resulting in attenuation of mitochondrial FA oxidation. Transgenic mice expressing ApoL6 in BAT exhibited a
lower thermogenic capacity upon cold exposure, and decreased energy expenditure along with increased
adiposity. Conversely, adipose ApoL6 knockout mice on HFD showed a decreased body weight and fat mass
gain. Based on these preliminary data, we hypothesize that by inhibiting mitochondrial FA oxidation and
thereby decreasing energy expenditure, ApoL6 plays a key role in (1) maintaining fat storage in WAT and
whole-body energy balance, and (2) impeding non-shivering thermogenesis in whitened BAT. There are three
aims: In aim 1, we will determine the mechanistic role of mitochondrially localized ApoL6 in adipocyte FA
oxidation by using gain- and loss-of-function cell models. In Aim 2 we will determine how adipose specific
ApoL6 ablation in mice affects diet-induced obesity and its related metabolic changes including insulin
resistance. In Aim 3 we will use both loss- and gain-of-function mouse models to define the role of ApoL6 in
the regulation of BAT thermogenesis during obesity- and thermoneutrality-induced whitening. Evidence derived
from this project should provide novel insight into the molecular basis for the regulation of FA oxidation and
energy metabolism in adipose tissue, thereby advancing the possibilities for the development of novel
therapeutic approaches to combat obesity and type 2 diabetes.

## Key facts

- **NIH application ID:** 10746791
- **Project number:** 5R01DK130331-03
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Jun Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $484,709
- **Award type:** 5
- **Project period:** 2021-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10746791

## Citation

> US National Institutes of Health, RePORTER application 10746791, Lipid metabolism and adipose tissue function (5R01DK130331-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10746791. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*