# Regulating energy expenditure in adipose tissue

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $545,100

## Abstract

Abstract
There is little doubt that we are in the midst of a worldwide epidemic of obesity and diabetes. Recent data
suggest an inflammatory link between obesity and insulin resistance. This proposal will focus on adaptive
changes in energy expenditure during caloric overload and restriction, and explore a novel hypothesis that may
directly lead to new therapeutic approaches. We hypothesize that that activation and induction of the protein
kinase TBK1 in obesity and fasting reprograms metabolism to promote anabolic and repress catabolic
pathways, tipping the scales towards energy storage and away from expenditure. These conclusions are derived
from changes observed in mouse knockout mice, and in patients treated with the TBK1 inhibitor amlexanox.
Specifically, activation or induction of TBK1 represses AMPK activity, inhibiting lipid oxidation and
mitochondrial biogenesis while increasing lipogenesis. We will explore this hypothesis with three aims: 1) We
will evaluate the temporal and spatial aspects of TBK1 activation and induction during obesity, and
characterize the underlying mechanism; 2) We will explore the activation and induction of TBK1 during fasting,
and elucidate the molecular mechanisms; 3) We will assess the role of the TBK1/AMPK axis in controlling
metabolism during obesity and fasting via development of compound knockout mouse models, and evaluate
the temporal and spatial aspects of this regulation. These findings may reveal how energy expenditure is
repressed during caloric excess and restriction, and provide new therapeutic approaches to these devastating
diseases.

## Key facts

- **NIH application ID:** 10434151
- **Project number:** 5R01DK124496-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** ALAN R. SALTIEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $545,100
- **Award type:** 5
- **Project period:** 2020-09-11 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10434151

## Citation

> US National Institutes of Health, RePORTER application 10434151, Regulating energy expenditure in adipose tissue (5R01DK124496-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10434151. Licensed CC0.

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