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Updated: Apr 19, 2026
Differentiation and Imaging of Brown Adipocytes from the Stromal Vascular Fraction of Interscapular Adipose Tissue from Newborn Mice
Published on: February 3, 2023
White-to-brown metabolic conversion of human adipocytes by JAK inhibition
Annie Moisan1, Youn-Kyoung Lee2, Jitao David Zhang1
1Roche Pharma Research and Early Development, Roche Innovation Center Basel, 124 Grenzacherstrasse, Basel CH 4070, Switzerland.
Abstract:
The rising incidence of obesity and related disorders such as diabetes and heart disease has focused considerable attention on the discovery of new therapeutics. One promising approach has been to increase the number or activity of brown-like adipocytes in white adipose depots, as this has been shown to prevent diet-induced obesity and reduce the incidence and severity of type 2 diabetes. Thus, the conversion of fat-storing cells into metabolically active thermogenic cells has become an appealing therapeutic strategy to combat obesity. Here, we report a screening platform for the identification of small molecules capable of promoting a white-to-brown metabolic conversion in human adipocytes. We identified two inhibitors of Janus kinase (JAK) activity with no precedent in adipose tissue biology that stably confer brown-like metabolic activity to white adipocytes. Importantly, these metabolically converted adipocytes exhibit elevated UCP1 expression and increased mitochondrial activity. We further found that repression of interferon signalling and activation of hedgehog signalling in JAK-inactivated adipocytes contributes to the metabolic conversion observed in these cells. Our findings highlight a previously unknown role for the JAK-STAT pathway in the control of adipocyte function and establish a platform to identify compounds for the treatment of obesity.
Insights
Scientists discovered two Janus kinase (JAK) inhibitors that convert white fat cells into brown-like cells, offering a new strategy for obesity treatment and metabolic disease prevention.
Area of Science:
- Metabolic research
- Obesity therapeutics
- Adipocyte biology
Background:
- Rising obesity and diabetes rates necessitate novel therapeutic strategies.
- Converting white adipocytes to brown-like cells is a promising approach to combat obesity and type 2 diabetes.
- Targeting adipocyte metabolism offers a potential therapeutic avenue for metabolic disorders.
Purpose of the Study:
- To develop a screening platform for identifying small molecules that promote white-to-brown adipocyte conversion.
- To identify novel compounds that can induce brown-like metabolic activity in human white adipocytes.
- To explore the role of signaling pathways in adipocyte metabolic reprogramming.
Main Methods:
- Development of a screening platform for human adipocytes.
- Identification and characterization of small molecule inhibitors of Janus kinase (JAK) activity.
- Assessment of UCP1 expression, mitochondrial activity, and signaling pathway modulation (interferon and hedgehog) in converted adipocytes.
Main Results:
- Two JAK inhibitors were identified that stably induce brown-like metabolic activity in white adipocytes.
- Metabolically converted adipocytes exhibited increased UCP1 expression and mitochondrial activity.
- JAK inhibition led to repression of interferon signaling and activation of hedgehog signaling, contributing to the observed metabolic conversion.
Conclusions:
- Janus kinase (JAK)-STAT pathway plays a previously unrecognized role in controlling adipocyte function.
- The identified JAK inhibitors represent potential therapeutic leads for obesity and related metabolic disorders.
- The developed screening platform can be utilized to discover further compounds for metabolic disease treatment.
