# Novel pathways in the pathogenesis and pathophysiology of NAFLD in Hispanics

> **NIH NIH R01** · OHIO UNIVERSITY ATHENS · 2020 · $704,221

## Abstract

Project Summary
Non-alcoholic fatty liver disease (NAFLD/NASH), the most common of liver pathologies in the US, varies widely
among races/ethnicities with higher rates in Hispanics than non-Hispanic Whites, making this disease one of the
most profound health disparities. In preliminary data, we have confirmed this health disparity using the NHANES
1988-1994 data base. In this proposal investigators from three institutions, Ohio University, Charles R. Drew
University and the University of Florida are collaborating to uncover the etiology of this health disparity by
delineating its epidemiological, cellular and molecular underpinnings. Obese subjects with NAFLD and insulin
resistance exhibit a lower level of hepatic CEACAM1, a protein that limits hepatic steatosis by promoting hepatic
insulin clearance and subsequently, preventing hyperinsulinemia-driven lipogenesis, and by mediating a
negative effect of acute release of insulin on fatty acid synthase activity in liver. Reduction of CEACAM1
expression is mediated by lipolysis-derived fatty acids activation of PPAR alpha. In preliminary RNASeq data
analysis, we show that the mRNA levels of CEACAM1 are significantly lower in the livers of Hispanic than non-
Hispanic White liver donors, in parallel to lower expression of PNPLA3 lipase that harbors a well-documented
mutation in NAFLD/NASH patients and Hispanics. We also show lower levels of CIDEC/FSP27, a protein that
interacts with the adipose triglyceride lipase to prevent lipolysis from adipoyctes, in the abdominal fat tissue (AT)
of Hispanics versus non-Hispanic Whites undergoing bariatric surgery. Given that CIDEC/FSP27 is reduced in
the abdominal AT of obese subjects, and because its mutation is associated with increased lipolysis in humans,
we hypothesize that Hispanics exhibit higher hepatic de novo lipogenesis and steatosis compared to non-
Hispanic Whites, and that this is mediated by reduced hepatic CEACAM1 expression that results from excess
free fatty acid flux during lipolysis, which is in turn caused by reduction of CIDEC level in abdominal adipose
tissue. To test this hypothesis, we will in Aim 1, use NHANES databases to identify the epidemiological
underpinnings of this health disparity. In Aim 2, we will delineate the role of the loss of CIDEC in AT in hepatic
steatosis in Hispanics. In Aim 3, we will investigate whether the loss of CIDEC in AT causes a decrease in
hepatic CEACAM1 in Hispanics in parallel to hepatic steatosis. Our approach is designed to study the adipose
tissue-liver cross-talk that plays a critical role in NAFLD disparity. A strength of this proposal is an interdisciplinary
collaboration between Drs. Ali Zarrinpar (liver transplant and hepatobiliary surgeon), Sonia M. Najjar (fatty liver
disease and lipid metabolism), Vishwajeet Puri (adipose biology and lipid metabolism) and Theodore Friedman
(hepatic steatosis and Health disparity in metabolic disease). As is clear from the strong preliminary data, these
scientist...

## Key facts

- **NIH application ID:** 9892028
- **Project number:** 5R01MD012579-02
- **Recipient organization:** OHIO UNIVERSITY ATHENS
- **Principal Investigator:** THEODORE C FRIEDMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $704,221
- **Award type:** 5
- **Project period:** 2019-03-12 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9892028

## Citation

> US National Institutes of Health, RePORTER application 9892028, Novel pathways in the pathogenesis and pathophysiology of NAFLD in Hispanics (5R01MD012579-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9892028. Licensed CC0.

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