# Metabolic Flux Analysis of Obesity-Associated Inflammation in Weight Loss

> **NIH NIH K08** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $170,316

## Abstract

ABSTRACT
Obesity is the most important preventable cause of disease in the United States, and its major complications
include insulin resistance/type 2 diabetes, coronary artery disease (CAD), and heart failure. The reasons for
these complications are not totally understood and assessment of patients before and after weight loss provides
the opportunity to dissect the factors that are improved with reduced body fat. Elevated white blood cell (WBC)
levels are a well-established CAD risk factor, while adipose tissue inflammation is considered an emerging risk
factor for the development of obesity complications. However, the beneficial effects of weight loss on these
inflammatory markers are not universal. Our recently published manuscript demonstrates how rapid diet-induced
weight loss improves insulin sensitivity while increasing adipose tissue inflammation in human subjects. The
proposed study will explore this dissociation and bariatric weight loss to seek mechanistic insight. We will
characterize human adipose tissue macrophage metabolism in the context of weight loss using an in-vitro
adipose tissue inflammation model (Aim 1). We will further assess changes in circulating WBC numbers and
phenotype with bariatric weight loss in metabolically healthy versus unhealthy obese subjects undergoing sleeve
gastrectomy (Aim 2), and concomitantly measure changes in adipose tissue inflammation (Aim 3) within six
weeks of this intervention. The central hypothesis of this research is that lipid signals from the adipocyte modulate
adipose tissue macrophage metabolism to prevent adipose tissue inflammation in weight loss. Consequently,
the nature of this metabolic queue will prevent or ameliorate the WAT inflammatory state. Antiinflammatory
macrophages are thought to maintain the integrity of healthy adipose tissue, while proinflammatory macrophages
are thought to be the hallmark cell in adipose tissue inflammation. The rationale that underlies this research is
that better understanding of the metabolic and immune cues that lead to white adipose tissue inflammation will
allow for the development of detection and therapeutic strategies for this cardiometabolic risk factor. To achieve
these aims, I will be supported by my primary mentor Dr. Ira Goldberg (NYULMC), a scientific leader in the study
of lipid metabolism and circulating inflammatory markers in metabolic disease, and my co-mentor with expertise
in the execution of detailed translational studies in the metabolic ward setting, Dr. Jan Breslow (Rockefeller
University). Each mentor will help me complete the individual aims of this project and develop the skills to pursue
my independent scientific program studying the immunometabolism of human adipose tissue during weight loss.

## Key facts

- **NIH application ID:** 10436211
- **Project number:** 5K08DK117064-04
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Jose Orlando Aleman
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $170,316
- **Award type:** 5
- **Project period:** 2019-09-04 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436211

## Citation

> US National Institutes of Health, RePORTER application 10436211, Metabolic Flux Analysis of Obesity-Associated Inflammation in Weight Loss (5K08DK117064-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10436211. Licensed CC0.

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