# Longitudinal Multi-Omic Profiles to Reveal Mechanisms of Obesity-Mediated Insulin Resistance

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $628,341

## Abstract

ABSTRACT
Overweight/obesity is a significant epidemic afflicting a majority of Americans, some of whom develop insulin
resistance (IR), which contributes to the development of type 2 diabetes mellitus (T2DM) and cardiovascular
disease (CVD). It remains a critical question why some individuals develop IR at modestly elevated body weight
and others can sustain substantial amounts of excess body fat while remaining insulin sensitive (IS). Prior studies
using GWAS have failed to fully explain this phenomenon. Focusing strictly on genetics, however, misses the
complex and lifelong effects of diet and environment on cellular function. To gain a more complete picture of the
IR process, our group proposes to apply a longitudinal multi-omic strategy of unprecedented depth for the
discovery of molecular changes associated with the development of IR using a human model for experimental
weight gain, followed by weight loss. We will measure biomolecules (transcripts, metabolites, proteins and
cytokines) in blood, adipose tissue, and muscle: 1) at baseline comparing IR to IS Individuals; 2) at peak weight
as compared to baseline and post weight loss; 3) compare changes in those individuals who experience
metabolic decline with weight gain vs those who exhibit metabolic tolerance of similar weight gain. We
hypothesize that through this dynamic intervention with longitudinal analysis we can elucidate biomolecules and
pathways that change in response to weight gain and loss and specifically that uniquely associate with IR
independent of weight or weight gain. These highly novel data that can be generated only by our group will
significantly expand our understanding of biomolecules and pathways that characterize and predict development
of the IR state, offering new markers for enhanced risk stratification (for adverse response to weight gain) and
therapeutic strategies that have potential for a major impact on preventing obesity-induced metabolic disease.

## Key facts

- **NIH application ID:** 9895799
- **Project number:** 5R01DK110186-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** TRACEY MCLAUGHLIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $628,341
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9895799

## Citation

> US National Institutes of Health, RePORTER application 9895799, Longitudinal Multi-Omic Profiles to Reveal Mechanisms of Obesity-Mediated Insulin Resistance (5R01DK110186-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9895799. Licensed CC0.

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