Systems biology reveals uncoupling beyond UCP1 in human white fat-derived beige adipocytes
Nyman E., Bartesaghi S., Melin Rydfalk R., Eng S., Pollard C., Gennemark P.
Laboratory Study, published in NPJ Syst Biol Appl (2017) — summary generated from the PubMed abstract.
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Laboratory Study
- Journal
- NPJ Syst Biol Appl (2017)
- Reported sample size
- —
- Source database
- Europe PMC
- PMID
- 28983409
- PMCID
- PMC5626775
- DOI
- 10.1038/s41540-017-0027-y
- Citations
- 14
Abstract (original English)
Pharmaceutical induction of metabolically active beige adipocytes in the normally energy storing white adipose tissue has potential to reduce obesity. Mitochondrial uncoupling in beige adipocytes, as in brown adipocytes, has been reported to occur via the uncoupling protein 1 (UCP1). However, several previous in vitro characterizations of human beige adipocytes have only measured UCP1 mRNA fold increase, and assumed a direct correlation with metabolic activity. Here, we provide an example of pharmaceutical induction of beige adipocytes, where increased mRNA levels of UCP1 are not translated into increased protein levels, and perform a thorough analysis of this example. We incorporate mRNA and protein levels of UCP1, time-resolved mitochondrial characterizations, and numerous perturbations, and analyze all data with a new fit-for-purpose mathematical model. The systematic analysis challenges the seemingly obvious experimental conclusion, i.e., that UCP1 is not active in the induced cells, and shows that hypothesis testing with iterative modeling and experimental work is needed to sort out the role of UCP1. The analyses demonstrate, for the first time, that the uncoupling capability of human beige adipocytes can be obtained without UCP1 activity. This finding thus opens the door to a new direction in drug discovery that targets obesity and its associated comorbidities. Furthermor
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • This is preclinical work; animal or laboratory results cannot be applied to humans.
Evidence level
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
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