# Bile acid composition and insulin sensitivity

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $642,294

## Abstract

PROJECT SUMMARY
Bile acid composition contributes strongly to metabolic regulation. The particular subset of bile acids that are
hydroxylated in the carbon 12? position (12HBAs) are negatively regulated by insulin signaling and
synthesized at higher rates in people with insulin resistance. People with low 12HBAs show improvements in
glucose and lipid metabolism, but the mechanisms of these effects are unknown. A longstanding barrier to
progress in understanding the mechanisms by which bile acid composition regulates systemic metabolism has
been the lack of a translationally relevant mouse model. But exciting recent progress in the field has uncovered
mouse models with humanized bile acid composition. In this grant, we will use humanized mice to dissect the
physiologic and molecular mechanisms by which bile acid composition, particularly 12HBAs, regulate lipid and
glucose metabolism. We will examine effects in the liver, the intestine, and the adipose tissue, three key
tissues where 12HBAs may carry out their differential effects. We will complement gold-standard in vivo mouse
studies with ex vivo and in vitro systems to isolate the cell autonomous effects of bile acid composition.
Success of this work will reveal fundamental mechanisms by which bile acid composition regulates metabolic
homeostasis and may inform pharmacologic attempts to specifically reduce 12HBAs for metabolic disease
treatment.

## Key facts

- **NIH application ID:** 10876364
- **Project number:** 5R01DK115825-07
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Rebecca Anne Haeusler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $642,294
- **Award type:** 5
- **Project period:** 2017-09-15 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876364

## Citation

> US National Institutes of Health, RePORTER application 10876364, Bile acid composition and insulin sensitivity (5R01DK115825-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10876364. Licensed CC0.

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