# Sympathetic Control of Liver Metabolism in Exercise and Obesity

> **NIH NIH K01** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $104,885

## Abstract

PROJECT SUMMARY
The prevalence of obesity and its complications, including diabetes and non-alcoholic fatty liver disease (NAFLD)
are a significant health care crisis. These complication impact liver metabolism by dysregulating
gluconeogenesis, lipid synthesis, mitochondrial function, and fat oxidation. NAFLD is improved by lifestyle
interventions. Ironically, physical activity, exercise, and aerobic capacity affect many of these pathways similarly,
but profoundly lower liver fat independent of weight loss. Hence, aerobic exercise is commonly prescribed
therapy for NAFLD. One route by which obesity or exercise influence regulation of liver metabolism may be by
signals through the sympathetic nervous system. The overarching goal of this 5-year research career
development plan is to facilitate my transition from a technically focused researcher to a fully independent
academic scientist investigating the in vivo physiology of disease. This will be accomplished by training in
disciplines of physiology, neurophysiology, and exercise that will be used to identify mechanisms by which
hepatic sympathetic nervous signaling controls liver metabolic flux during obesity and interventions. Elevated
basal sympathetic signaling is thought to occur through the α1b adrenergic receptor (AR), which is highly
expressed in mouse liver (including hepatocytes) and has been suggested to stimulate hepatic glucose
production, breakdown of glycogen, gluconeogenesis, tricarboxylic acid (TCA) cycle and ketogenesis. This
project focuses on understanding how hepatic α1b-AR contributes to dysregulated hepatic gluconeogenesis and
fat oxidation during obesity and NAFLD (Aim 1), and the degree to which liver α1b-AR mediates beneficial effects
of acute (Aim 2) or chronic exercise (Aim 3) as treatments of NAFLD. Using targeted metabolomics and stable
isotope infusions, I will quantitatively evaluate how AR signaling regulates liver metabolism. The findings will
advance our knowledge of how metabolism is altered by complications of obesity and provide a novel training
platform for the recipient.

## Key facts

- **NIH application ID:** 10506749
- **Project number:** 1K01DK133630-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Stanislaw Marek Deja
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $104,885
- **Award type:** 1
- **Project period:** 2022-07-07 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10506749

## Citation

> US National Institutes of Health, RePORTER application 10506749, Sympathetic Control of Liver Metabolism in Exercise and Obesity (1K01DK133630-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10506749. Licensed CC0.

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