# Adipose Mitochondial Quality Control and Cardiovascular Function in Metabolically Healthy and Unhealthy Obese Monkeys

> **NIH NIH R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2020 · $689,686

## Abstract

Summary
Controversy exists regarding the metabolically healthy obese (MHO) classification, whether it is a transient
state that precedes the development of cardiometabolic disease, or whether these individuals have preferred
biological handling of excess adipose tissue (AT). We have documented the first spontaneous monkey model
of MHO and unhealthy (MUO) obesity. Monkeys have near identical prevalence of MHO and MUO as well as
healthy and healthy lean individuals (MHL/MUL) as humans, and are an excellent model of cardiovascular
disease (CVD) and diabetes. Monkey MUO subcutaneous AT (SAT) has deficits in mitochondrial quality
control and redistribution towards inflammatory M1-macrophages. We hypothesize that inadequate
mitochondrial metabolism in SAT leads to greater ectopic fat accumulation and inflammation which drives the
development of cardiometabolic diseases. It is unknown if these AT characteristics are observed in visceral
adipose tissue (VAT) and if it is conserved across AT depots and over time. A related gap in knowledge is if AT
in MUO shifts with weight loss towards improved mitochondrial function and a redistribution to include more
anti-inflammatory M2-type macrophages, similar to that observed in the MHO state. We aim to answer
questions pertaining to the generalizability of fat characteristics across AT depots in MHO/MHL and
MUO/MUL, the stability of these phenotypes under caloric restriction, and persistence of these phenotypes in
offspring that are genetically programmed for obesity. Our aims and outcomes are: 1. Characterize AT
distribution and quality in lean and obese health-diverse monkeys. Surgical biopsies of SAT, VAT and liver will
enable assessment of AT quality measures in MHO/MHL/MUO/MUL adult monkeys. We will quantitate
mitochondrial bioenergetics, quality control and structure, inflammatory cell populations, gene expression
profiles, cytokines, fibrosis, vascularity, fat density and distribution across sites in the body. Liver fat and
histology will be additionally measured. Differences in AT quality will also be related to a novel outcome,
peripheral blood mononuclear cell (PBMC) energetics; 2. Evaluate AT phenotypic stability and relate AT
changes after weight loss to CVD risk and novel biomarkers. Repeated AT quality measures, PBMC
bioenergetics before and after caloric restriction to achieve ≥10% weight loss will be performed. Changes will
be related to changes in magnetic resonance imaging for CVD structure and function, biomarkers and MetS
scores. 3. Document pre-obesity AT characteristics and biomarkers in at-risk youth. We will evaluate juvenile
monkeys (2 and 3 year olds; puberty≈4 years) with the above-listed AT quality evaluations. Juveniles will be re-
assessed as young adults for AT quality and health measures after weight gain. At completion we will have
addressed gaps in knowledge about AT depots and health in a relevant animal model that is un-confounded by
variable dietary and environmental influence...

## Key facts

- **NIH application ID:** 9838815
- **Project number:** 5R01HL142930-02
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Kylie Kavanagh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $689,686
- **Award type:** 5
- **Project period:** 2018-12-15 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9838815

## Citation

> US National Institutes of Health, RePORTER application 9838815, Adipose Mitochondial Quality Control and Cardiovascular Function in Metabolically Healthy and Unhealthy Obese Monkeys (5R01HL142930-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9838815. Licensed CC0.

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