# Metabolic impact of FGF-21 in adipose tissue and liver of PLWH

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2022 · $655,060

## Abstract

ABSTRACT
HIV and antiretroviral therapy (ART) are associated with adipose tissue (AT) dysfunction and
systemic metabolic alterations, including intra-abdominal fat accumulation, fatty liver disease,
dyslipidemia, and insulin resistance. Treatment of these defects using conventional drugs and
lifestyle interventions has been minimally effective. Viral factors and ART contribute to the
complex pathophysiology of these disease states in persons living with HIV (PLWH). Still, the
mechanisms that link viral factors and ART to defective AT and hepatic metabolism remain
incompletely understood. We have demonstrated in mouse models that the HIV accessory
protein Vpr is sufficient to cause all the cardinal manifestations of HIV-associated metabolic
disease. The Vpr mice also have high levels of FGF21 and increased subcutaneous AT
thermogenesis. The current proposal aims to establish mechanistic connections between
increased FGF21 levels, white AT thermogenesis, and the observed metabolic abnormalities in
Vpr mice and PLWH. Our central hypothesis is that Vpr expression alters the metabolic effects
of FGF21, altering AT and hepatic function and inducing maladaptive browning of subcutaneous
white AT. We will test this hypothesis by achieving the following Specific Aims: 1) Determine
how Vpr exposure affects white AT thermogenesis in mice; 2) Demonstrate how FGF21 shapes
the metabolic abnormalities of Vpr mice; 3) Establish relationships between FGF21’s endocrine
actions and defects of lipid and glucose metabolism and subcutaneous white AT function in
PLWH on suppressive ART. Our research plan will provide detailed dissection of the
relationships between HIV-associated metabolic disease and FGF21 physiology, molecular
mechanisms of thermogenesis and AT physiology, and immunology. The project will reveal
mechanisms of unique metabolic defects in Vpr mouse models that recapitulate those in PLWH,
and elucidate how FGF21’s endocrine functions contribute to HIV-associated metabolic
abnormalities in PLWH on ART. Ultimately, this translational work will identify mechanisms of
HIV-specific metabolic alterations and may identify therapeutic targets that can be exploited to
minimize the long-term clinical burden of metabolic disease in PLWH.

## Key facts

- **NIH application ID:** 10434945
- **Project number:** 5R01DK126042-03
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Jordan E Lake
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $655,060
- **Award type:** 5
- **Project period:** 2020-09-10 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10434945

## Citation

> US National Institutes of Health, RePORTER application 10434945, Metabolic impact of FGF-21 in adipose tissue and liver of PLWH (5R01DK126042-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10434945. Licensed CC0.

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