# Novel Adipocyte Engineering Technology for Modeling Adipocyte Dysfunction in Human Obesity

> **NIH NIH R43** · MELLICELL, INC. · 2024 · $295,923

## Abstract

PROJECT SUMMARY
The increasing global prevalence of obesity and its association with diabetes motivate a need for mechanistic
understanding of pathogenesis. Obesity is a complex, multifactorial disease with contributions from the control
circuitry of appetite and energy expenditure in the brain and critical endocrine and metabolic signals from
peripheral organs including fat tissue. At the cellular level, dramatic changes in fat cell structure and function are
defining features of obesity, and link obesity to insulin resistance through mediators including leptin, adiponectin,
and proinflammatory lipids and cytokines. While appetite reduction has appropriately received a great deal of
attention in obesity research resulting in the recent approval of multiple GLP1 drugs for obesity, mechanistic
understanding of the contributions of fat tissue and therapeutic progress toward increasing energy expenditure
has had limited success. A major reason for this lack of therapeutic progress is that the pharmaceutical industry
lacks scalable drug discovery tools for testing drugs or determining mechanisms of action in mature human fat
cells. The overarching goal of the current R43 Phase I application is to demonstrate how MelliCell’s proprietary
M3 platform can generate normal and obese-like fat cells that closely mimic ex vivo mature fat cells relative to
immature fat cells derived from the conventional two-dimensional (2D) method. To test this, we collaborate with
Brigham and Women’s Hospital and propose two specific milestones. In Milestone 1, we will compare the
differentiation efficiency, lipid droplet size, insulin sensitivity, cytokine and hormone secretion in ex vivo vs. M3
and 2D vs. M3 fat cells, obtained from the same donor. The results from this aim will quantitatively evaluate the
robustness of M3 technology by displaying phenotypic features and functional readouts like those exhibited by
mature ex vivo fat cells. In Milestone 2, considering the variety of fat-cell derived biomarkers for obesity, we will
use state-of-the-art multiomics to demonstrate the ability of M3 technology to differentiate donors with versus
without obesity. Parameters for testing will include multi-feature imaging, mRNA/protein quantification, endocrine
function, and lipolysis and glucose uptake assays. Common disease associated genetic variants known to be highly
prevalent (for example, CAV1 single nucleotide variants or SNVs) will also be analyzed to further classify
phenotypes in M3 adipocytes. Completion of this Phase I study will establish the generation of a novel fat cell
engineering technology with direct comparison to in vivo tissue for modeling human pathology. Progression to
Phase II will facilitate expanded testing of obesity-linked SNPs to capture donor specific responses to disease
relevant stimuli, enabling the development of therapeutics with potential to reverse the metabolic dysfunction in
fat cells in obesity that leads to insulin resistance and diabetes.

## Key facts

- **NIH application ID:** 10924548
- **Project number:** 1R43DK137676-01A1
- **Recipient organization:** MELLICELL, INC.
- **Principal Investigator:** Madhumita Basu
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $295,923
- **Award type:** 1
- **Project period:** 2024-05-09 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10924548

## Citation

> US National Institutes of Health, RePORTER application 10924548, Novel Adipocyte Engineering Technology for Modeling Adipocyte Dysfunction in Human Obesity (1R43DK137676-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10924548. Licensed CC0.

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