# Bile acids and insulin sensitivity

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $189,111

## Abstract

PROJECT SUMMARY
Bile acid (BA) signaling pathways are plausible new therapeutic targets for metabolic disease. One potential
approach is to improve the composition of endogenous BAs. Humans have dozens of species of BAs, and
each is differently able to carry out BA functions. We have previously identified a subset of BAs–those
containing a hydroxyl group at the carbon 12 position–that are regulated by hepatic insulin signaling, increased
in human insulin resistance, and correlated with metabolic dysfunctions. Eliminating 12-hydroxy BAs by
ablating the enzyme required for their synthesis, Cyp8b1, lowers body weight, lipids, and glucose. However the
molecular mechanisms of these improvements are incompletely understood, particularly the mechanisms
leading to improved glycemia. Thus we have identified three fundamental, unanswered questions for our
studies: First, what signaling pathways are required to bring about these improvements? Second, what are the
direct effects of 12-hydroxy BAs on cellular metabolic and signaling cascades? Third, what are the metabolic
benefits of eliminating 12-hydroxy BAs in pre-existing diabetes/obesity? These questions will be addressed in
vivo and ex vivo, using genetic, biochemical, and humanized tools. The proposed studies will improve our
understanding of this conserved enzyme in physiology and its potential as a new therapeutic strategy.

## Key facts

- **NIH application ID:** 10221090
- **Project number:** 3R01DK115825-03S1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Rebecca Anne Haeusler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $189,111
- **Award type:** 3
- **Project period:** 2018-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10221090

## Citation

> US National Institutes of Health, RePORTER application 10221090, Bile acids and insulin sensitivity (3R01DK115825-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10221090. Licensed CC0.

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