# Effects of Palmitic Acid esters of Hydroxy Stearic Acids (PAHSAs) on intestinal mucosal biology for the treatment of Type 2 Diabetes

> **NIH NIH K01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $40,500

## Abstract

PROJECT SUMMARY/ABSTRACT:
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. Compelling 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. The 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) determine the contribution of the gut microbiota in mediating PAHSA
effects on gut barrier function and glucose metabolism. Gnotobiotic and immunodeficient mouse models,
adoptive transfer of immune and microbial cells, assessment of insulin sensitivity, and sophisticated
immunology techniques will be used to determine the functional contribution of intestinal immune responses
and the gut microbiota in regulating beneficial PAHSA effects on glucose metabolism. Mentorship of this
innovative research proposal is led by Dr. Barbara Kahn, a leader in the field of diabetes research. Dr. Kahn
will provide expertise in glucose homeostasis. Dr. Diane Mathis, a renowned immunologist and expert in T-cell
immune responses, will serve as co-mentor and will provide vital expertise in immunology. Multidisciplinary
expertise and guidance from Dr. Lee’s Academic Advisory Committee will provide an unparalleled environment
to develop and foster Dr. Lee’s scientific and academic career goals. This K01 will extend Dr. Lee’s training
experience in endocrine gut physiology and develop her expertise in gut immunology and microbiology in the
context of metabolic disease. The strong mentorship team, structured training plan, and innovative research
proposal will successfully foster Dr. Lee’s long-term career goal of developing an independent research
program in diabetes and metabolism. This research proposal will define the mechanisms by which PAHSAs
improve gut mucosal homeostasis which will identify novel therapeutic strategies to treat obesity and T2D.

## Key facts

- **NIH application ID:** 10219652
- **Project number:** 3K01DK114162-03S1
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Jennifer Lee
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $40,500
- **Award type:** 3
- **Project period:** 2018-04-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219652

## Citation

> US National Institutes of Health, RePORTER application 10219652, Effects of Palmitic Acid esters of Hydroxy Stearic Acids (PAHSAs) on intestinal mucosal biology for the treatment of Type 2 Diabetes (3K01DK114162-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10219652. Licensed CC0.

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