# The role of impaired adipogenesis in insulin resistance among non-obese individuals

**Authors:** Shamma Almuraikhy, Maha Alser, Khaled Naja, Najeha Anwardeen, Samir Taha, Jomon John, Sharique Halim, Saif Badran, Mohamed Badie Ahmed, Salma Jarrar, Ghanem Aljassem, Fatima Saoud Al-Mohannadi, Suhail Doi, Asmaa Abdel-Aziz, Yousra Jalal Elaf, Mohamed A. Elrayess

PMC · DOI: 10.3389/fphys.2025.1739215 · Frontiers in Physiology · 2026-01-07

## TL;DR

This study explores how poor fat cell development contributes to insulin resistance in non-obese people, suggesting new treatment approaches.

## Contribution

The study reveals impaired adipogenesis as a key factor in insulin resistance among non-obese individuals, expanding beyond obesity-related mechanisms.

## Key findings

- Insulin-resistant non-obese individuals showed reduced adipogenic capacity compared to insulin-sensitive individuals.
- Insulin-resistant participants exhibited increased susceptibility to TNF-α-induced anti-adipogenic effects and inflammation.
- Hyperphosphorylation of insulin receptor substrate-1 may underlie the observed adipogenesis impairment.

## Abstract

Adipogenesis is an essential process for energy storage, hormone regulation, and overall metabolic health. Previous work showed that impaired adipogenesis plays an important role in the development of obesity-associated insulin resistance. This project investigates the role of impaired adipogenesis in the development of insulin resistance among non-obese (lean/overweight) individuals under physiological and pathological microenvironments.

Subcutaneous adipose tissue samples were obtained from insulin-sensitive and insulin-resistant non-obese cohorts undergoing maxillofacial or body contouring surgeries. Preadipocytes were isolated and examined for proliferation and adipogenic capacity, insulin signaling, and inflammatory markers. These assessments were conducted under basal conditions and following treatment with either tumor necrosis factor alpha (TNF-α) to induce insulin resistance or metformin to promote insulin sensitivity.

Insulin-resistant participants, in comparison to insulin-sensitive counterparts, showed lower adipogenic capacity, higher susceptibility to the anti-adipogenic and pro-inflammatory effect of TNF-α potentially due to hyperphosphorylation of insulin receptor substrate-1.

This highlights the role of impaired adipogenesis in the pathogenesis of insulin resistance among non-obese individuals. Further research is needed to understand the impact of impaired adipogenesis and the potential therapeutic interventions targeting adipogenesis to improve insulin sensitivity in non-obese individuals.

## Linked entities

- **Chemicals:** metformin (PubChem CID 4091), tumor necrosis factor alpha (PubChem CID 44356648)

## Full-text entities

- **Genes:** IRS1 (insulin receptor substrate 1) [NCBI Gene 3667] {aka HIRS-1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}
- **Diseases:** obese (MESH:D009765), inflammatory (MESH:D007249), overweight (MESH:D050177), insulin resistance (MESH:D007333)
- **Chemicals:** metformin (MESH:D008687)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12819270/full.md

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12819270/full.md

## References

29 references — full list in the complete paper: https://tomesphere.com/paper/PMC12819270/full.md

---
Source: https://tomesphere.com/paper/PMC12819270