# Effects of Palmitic Acid Hydroxy Stearic Acids (PAHSAs) on Intestinal Mucosal Biology for the Treatment of Type 2 Diabetes

> **NIH NIH K01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2021 · $76,874

## Abstract

OMB No. 0925-0001 (Rev. 03/2020 Approved Through 02/28/2023)
Project Summary
 Obesity-induced inflammation contributes to the development of insulin resistance and Type 2 Diabetes
(T2D). The gut plays an important yet poorly understood role in the development of T2D. Mounting evidence
implicates impaired intestinal immune responses and dysbiosis of the gut microbiota in driving the onset of insulin
resistance. Recently, a novel family of lipids called Palmitic Acid Hydroxy Stearic Acids (PAHSAs) was
discovered that are anti-inflammatory and anti-diabetic. Preliminary data demonstrates that PAHSAs improve
glucose homeostasis in insulin-resistant mice and this is associated with reduced intestinal inflammation and
favorable shifts to gut microbial species that associate with leanness. Functional analyses of the cecal
metabolome and metagenome from mice treated with PAHSA lipids has identified a probiotic that strongly
associates with insulin sensitivity in these same mice. Daily oral supplementation with this probiotic has beneficial
effects to reduce body weight gain and improve glucose homeostasis in conventional chow and high fat diet
(HFD)-fed mice. Our central hypothesis is that the gut plays an important role in mediating the beneficial effects
of PAHSAs on glucose homeostasis. The goals of this proposal are to 1) identify whether PAHSA effects on
improved gut barrier function and glucose metabolism are mediated by gut T-cells, and 2) defining the cecal and
serum metabolome from mice supplemented with the gut microbe that associates with insulin sensitivity in
PAHSA-treated mice. This grant will define the mechanisms by which PAHSAs and beneficial gut microbes
improve gut mucosal homeostasis and contribute to regulating glucose metabolism. These studies may reveal
novel therapeutic strategies and targets that beneficially leverage gut immune responses and the gut microbiome
to treat obesity and insulin resistance in humans.

## Key facts

- **NIH application ID:** 10382051
- **Project number:** 3K01DK114162-03S2
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Jennifer Lee
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $76,874
- **Award type:** 3
- **Project period:** 2018-04-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10382051

## Citation

> US National Institutes of Health, RePORTER application 10382051, Effects of Palmitic Acid Hydroxy Stearic Acids (PAHSAs) on Intestinal Mucosal Biology for the Treatment of Type 2 Diabetes (3K01DK114162-03S2). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10382051. Licensed CC0.

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