Reprogramming Human Adipocytes to Enhance Glucose Utilization
Cellular Reprogramming of Human Primary Adipocytes into Brown Adipose Tissue-Like Cells Preferentially Utilize Glucose
Taylor SRT1, Cartwright KM1, Sorrells AM1, and Harding P A1,*
Department of Biology, Cell Molecular and Structural Biology Program, Miami University, Oxford, OH 45056, United States
OPEN ACCESS
PUBLISHED:25, July 2025
CITATION:SR, Taylor et al. Cellular Reprogramming of Human Primary Adipocytes into Brown Adipose Tissue-Like Cells Preferentially Utilize Glucose. Medical Research Archives, [S.l.], v. 13, n. 7, july 2025. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/6709>. Date accessed: 14 sep. 2025.
COPYRIGHT:©2025 European society of medicine. This is an open- access article distributed under the term of creative commons attribution license,which permit unrestricted use, distribution, and reproduction in any meduim provided the original authors and source are credited.
DOI: https://doi.org/10.18103/mra.v13i7.6709.
ISSN 2375-1924
ABSTRACT
Brown adipose tissue has emerged as a potential therapeutic target for the treatment of type 2 diabetes and obesity. This aim of this study is to investigate how the expression of a disintegrin and metalloproteinase 12 (ADAM 12) expression alone in human primary adipocytes can drive the reprogramming of white adipocytes into metabolically active BAT-like cells through endogenous HB-EGF signaling. Such reprogramming could lay the groundwork for novel therapeutic strategies aimed at increasing energy expenditure, reducing fat mass, and addressing the metabolic conditions associated with obesity and type 2 diabetes.
Keywords: brown adipose tissue, adipocytes, glucose utilization, ADAM 12, metabolic disorders
Introduction
Obesity remains one of the most significant public health challenges, with rising prevalence rates where the increased availability of calorie-dense foods and a sedentary lifestyle have contributed to its rising prevalence. Defined by a body mass index (BMI) of 30 kg/m2 or higher, obesity is strongly associated with serious health conditions such as type 2 diabetes, cardiovascular diseases, and certain cancers. This growing epidemic not only impacts individual health but also places a tremendous burden on healthcare systems worldwide, resulting in escalating healthcare costs.
This study investigates the role of ADAM 12 in the reprogramming of human primary adipocytes into metabolically active BAT-like cells, independent of HB-EGF co-expression, and aims to elucidate the underlying mechanisms that drive this process.
Materials and Methods
Human primary adipocytes used in this study was generated using the AdAM12 adenovirus (Agilent Technologies, Santa Clara, CA). The AdAM12 expression vector (2.1 kb) was cloned into the pShuttle-1/Ad5-NGFP1.1 plasmid and transfected into HEK 293 cells, and resulted in non-infectious adenovirus.
qPCR IN HUMAN PRIMARY PREADIPOCYTES
For quantitative PCR (qPCR), total RNA from AdAM 12S and Ad-MOCK infected cells was reverse-transcribed into cDNA using a high-capacity cDNA reverse transcription kit (Applied Biosystems). qPCR was conducted using a SYBR Green RT-PCR Kit (Quantabio) on a CFX Connect Real-Time PCR Detection System (BioRad). The relative expression of brown adipose tissue (BAT) marker genes PRDM16, PGC-1α, UCP-1, and GAPDH was analyzed.
Table 1. Human primer sequences for all PCR and qPCR analyses.
| Gene Name | Primer Sequence for all PCR and qPCR |
|---|---|
| PRDM16 | GGAAGTGCCTGACCTGAC |
| UCP-1 | CTGTTCCATCAGCCTGAC |
| β-actin | TCCTCCTGAGCGCAAGT |
| GAPDH | CCCTGTTGCTGTAGCCAA |
| PPARγ | CCAGATGTTGCCCTGCTG |
| HB-EGF | ACGATGTCGCCCTGCGC |
Table 2. Differential Gene Expression in Human Primary Preadipocytes.
| Gene Name | Fold Change | P-value |
|---|---|---|
| PRDM16 | -2.40 | 0.0008 |
| UCP-1 | -2.31 | 0.0010 |
| PGC-1α | -2.10 | 0.0018 |
Discussion
According to the World Health Organization, 1 in 8 people in the world were living with obesity in 2015. The lipid accumulation is a characteristic feature of brown adipocytes, which store fuel for thermogenesis in the form of multilocular triglyceride droplets. Oil Red O staining confirmed the presence of lipids in ADAM 12S-infected cells, while mock-infected cells showed no such accumulation, consistent with previous findings in transgenic mice expressing ADAM 12S.
The ability of ADAM 12S to reprogram human primary preadipocytes into metabolically active BAT-like cells has significant therapeutic potential. Future research will further explore the mechanisms underlying adipocyte reprogramming and explore the therapeutic efficacy of this approach.
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