Diabetes research and clinical practiceSep 4, 2020

Lower UCP-1 levels in fat cells made from stem cells of type 2 diabetes patients are linked to buildup of harmful molecules in mitochondria during obesity

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 27, 2026

Abstract

Decreased UCP-1 expression in beige adipocytes was observed in patients with type 2 diabetes mellitus (T2DM).

Subcutaneous adipose-derived stem cells (ADSC) were isolated from patients with obesity and classified based on glucose tolerance status.
Beige adipocytes from T2DM patients exhibited equal lipolysis signaling and expression compared to those from patients with normal glucose tolerance.
No statistically significant differences were found in the expression of electron transport chain genes between beige adipocytes from both patient groups.
Increased mitochondrial reactive oxygen species (ROS) production was noted in beige adipocytes from T2DM patients during differentiation.
Compromised UCP-1 expression in T2DM beige adipocytes may lead to elevated mitochondrial ROS, potentially contributing to insulin resistance.

Simplified

OBJECTIVE: Adipose derived stem cells (ADSC) are defective in metabolic disorders in various functionalities and properties including differentiation, multipotent state, metabolism and immunomodulation. However, the role of ADSC beiging potential in promoting of type 2 diabetes mellitus (T2DM) development remains unclear. Here we uncover association between potential of subcutaneous ADSC to beige differentiation and T2DM in patients with obesity.

METHODS: ADSC were isolated from subcutaneous adipose tissue of patients with long morbid obesity (BMI > 35 kg/m2) and normal glucose tolerance (NGT) or T2DM. ADSC were differentiated into white or beige adipocytes and levels of thermogenic markers, lipid metabolism and electron transport chain (ETC) genes was analyzed by Western blotting and RT-PCR. ROS production was estimated by fluorescent microscopy.

RESULTS: We have shown decreased UCP-1 expression in beige adipocytes from T2DM patients. Nevertheless, signal and expression activities of lipolysis were equal in NGT and T2DM beige adipocytes. Expression analysis of ETC genes also has not shown any statistically significant differences. Interestingly, we revealed increased mitochondrial ROS production in T2DM beige adipocytes during beige differentiation.

CONCLUSIONS: In summary, compromised UCP1 expression in beige adipocytes of T2DM patients may cause increase of mitochondrial ROS. Elevated oxidative level is liable to act as damaging mechanism leading to insulin resistance or, alternatively, serve as compensatory mechanism for thermogenesis activation.

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Competing interests

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

PubMed

Lower UCP-1 levels in fat cells made from stem cells of type 2 diabetes patients are linked to buildup of harmful molecules in mitochondria during obesity

Abstract

Full Text

Funding

Competing interests

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