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Gene Analysis Research Uncovered a Physiological Brake Protecting Thermogenesis in Fat Tissue

Investigating cellular and molecular mechanisms to convert white adipocytes into brown-like adipocytes as a potential Type 2 diabetes therapy

Date Posted: Monday, January 03, 2022

 

lei-huang-adipose
Lei Huang, PhD

The human body contains several different types of fat, and not all fat is “bad.” Each type of fat, or adipose tissue, serves a unique role. Some promote healthy metabolism and hormone levels, while others negatively impact the body.

White adipose tissue is used for energy storage, but too much abdominal white fat can lead to Type 2 diabetes, heart disease, and other metabolic diseases. White adipose tissue acts as a thermal insulator, helping to maintain body temperature.

Brown adipose tissue is a special type of body fat that’s activated when the body becomes cold. As brown fat burns it creates heat through a process called thermogenesis, during which brown fat also burns calories.

The laboratory of Yong-Xu Wang, PhD, at UMass Chan Medical School, is focused on cellular and molecular mechanisms to convert white adipocytes into brown-like adipocytes, which could potentially provide therapeutic benefits to people with Type 2 diabetes, obesity and associated metabolic diseases.

Their lab focuses on transcriptional control, epigenetics, non-coding RNAs, and signaling molecules.  Adipose thermogenesis plays a pivotal role in whole-body metabolic homeostasis. Although transcriptional mechanisms that promote thermogenesis are extensively studied, the negative regulatory network is still poorly understood.

In a newly published manuscript in Advanced Science, the Wang lab identified a Krüppel-associated box (KRAB) domain-containing zinc finger protein, ZFP961, as a potent repressor of the thermogenic program. 

“Our study uncovered that Krüppel-associated box domain-containing zinc finger protein ZFP961 serves as a critical physiological brake to safeguard adipose thermogenesis,” said Lei Huang, PhD an instructor in the Wang lab. “We provided new insights into the negative feedback mechanisms that sustain whole-body energy balance and tissue homeostasis.” 

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The KRAB Domain-Containing Protein ZFP961 Represses Adipose Thermogenesis and Energy Expenditure through Interaction with PPARα


Lei Huang, Pengpeng Liu, Qiyuan Yang, Yong-Xu Wang
PMID: 34747141 DOI: 10.1002/advs.202102949

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