# Feasibility of a novel nonhuman primate model of age-related nonalcoholic fatty liver disease

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2021 · $193,333

## Abstract

ABSTRACT: Aging increases the prevalence of nonalcoholic fatty liver disease (NAFLD) which is escalating
markedly in the United States. NAFLD includes a spectrum of disorders ranging from hepatic steatosis to
steatohepatitis and even hepatocellular carcinoma in individuals who do not have a history of alcohol abuse.
NAFLD is also a rapidly rising indication for liver transplantation and is strongly associated with cardiovascular
disease (CVD), which is the leading cause of death in these patients. Pathogenetic mechanisms involved in
the development and progression of NAFLD are poorly understood and better mechanistic understanding
could help identify new approaches for effective therapies. Previous studies delineating mechanisms involved
in NAFLD have largely used rodent models which demonstrated that hepatic steatosis and activation of the
mechanistic target of rapamycin (mTOR) pathway increases with aging. Unfortunately, rodents fail to
recapitulate many of the features of this naturally-occurring human disease. The common marmosets
(Callithrix jacchus) are small, short-lived nonhuman primates (NHP), which have a more analogous physiology
to humans making them more suitable to elucidate mechanisms involved in the development of human
disease, particularly with aging. Our group is currently testing whether rapamycin, an inhibitor of mTOR, can
extend lifespan and improve healthy aging in the marmoset. A single study has previously reported NAFLD in
marmosets; however, the design of this study made it challenging to interpret effects of the naturally-occurring
disease in this model. Our aging marmoset cohort provides a unique well-controlled model for studying the
effects of aging on NAFLD that cannot be performed in humans or rodents. Moreover, for the first time we can
investigate the role of mTOR (through inhibition by rapamycin) on the progression of this disease in NHP, a
major step in bridging the knowledge gap in translational potential. We hypothesize that hepatic steatosis and
serum biomarkers of aberrant lipid metabolism and NAFLD in marmosets increase with aging and an anti-
aging intervention can prevent or delay the development of NAFLD. To test our hypothesis, we propose the
following: Specific Aim 1) To determine the extent to which alterations in hepatic steatosis and structure, and
changes in lipid metabolism occur with age in the common marmoset. Specific Aim 2) To elucidate the extent
to which a pharmaceutical intervention to the aging process affects the development of NAFLD in the
marmoset. Liver and cardiac imaging as well as serum lipidomics and biomarkers of NAFLD will be measured
in young and old marmosets, and the results compared with those in old marmosets treated with an anti-aging
intervention rapamycin. Significance and Innovation: Results of the proposed studies will provide insights
into the underlying mechanisms of aging and development of NAFLD. The successful establishment of this
unique NHP model of age-related...

## Key facts

- **NIH application ID:** 10147844
- **Project number:** 5R21AG067164-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** AMRITA KAMAT
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $193,333
- **Award type:** 5
- **Project period:** 2020-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10147844

## Citation

> US National Institutes of Health, RePORTER application 10147844, Feasibility of a novel nonhuman primate model of age-related nonalcoholic fatty liver disease (5R21AG067164-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10147844. Licensed CC0.

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