*For medical professionals only
Fat in the human body is mainly divided into brown fat (BAT), which is responsible for consuming lipids to produce calories, and white fats (WAT), which is responsible for storing lipids in case of unpreparedness.
Obviously, for the sake of weight loss and metabolic health, brown fat is much more sought-after than white fat. But as the exploration deepened, scientists found that brown fat doesn't seem to be all treasures, because some brown fat cells don't actually produce heat as expected, called low-thermogenic brown fat cells. Under environmental stimuli such as cold, low-thermogenic brown adipocytes can be transformed into high-thermogenic brown adipocytes.
Meilian Liu and her colleagues at the University of New Mexico Health Sciences Center in the United States have found a way to "wake up" brown fat cells with low heat production.
They found that adipocytes rich in the transcription factor JunB within brown fat exhibited lower thermogenesis and were more abundant in response to obesity induced by a high-fat diet. Depletion of JunB in adipocytes can increase the proportion of thermogenic brown adipocytes, improve energy expenditure, and prevent diet-induced obesity and insulin resistance[1].
The article was recently published in the journal Nature Metabolism.
Screenshot of the first page of the paper
The transcription factor JunB plays a key role in a variety of physiological processes, including placental formation, bone formation, cell proliferation, inflammation, and skin homeostasis. In this study, Meilian Liu et al. accidentally found JunB when they were exploring the mechanism of fat thermogenesis based on existing clues.
Previous studies have shown that mammalian rapamycin target protein complex 1 (mTORC1) is able to modulate the thermogenesis of brown and white fats. When exploring the intracellular signaling pathway downstream of mTORC1, the researchers found that the expression of protein JunB was affected by the activity of mTORC1, and the expression of JunB was inhibited when mTORC1 was inactivated, suggesting that JunB has a potential role in regulating the function and metabolism of adipocytes.
So, the researchers launched an investigation into JunB.
The results showed that the expression level of JunB was negatively correlated with the expression of UCP1 and PGC-1α, which are thermogenesis markers of deep neck fat, and positively correlated with fat mass/body mass index. The same is true in mice.
In addition, they used mouse experiments to find that JunB was selectively expressed in brown fat compared to white fat. More importantly, high-fat diet feeding can significantly increase the number of JunB-expressing adipocytes in brown fat in mice by inducing obesity-related pro-inflammatory states, and the proportion of Adipocytes expressing JunB in mice increased from 8.7% to 24.9% after 4 weeks of high-fat diet feeding.
It seems that JunB is inseparable from obesity.
The high-fat diet resulted in a greatly increased increase in the number of fat cells expressing JunB in brown fat
Knowing that the thermogenic capacity of brown fat is potentially important for maintaining energy balance and preventing obesity, activating and enhancing the thermogenic function of brown fat is a promising anti-obesity strategy. How exactly does JunB do his hands on brown fat?
Based on gene expression characteristics, the researchers found that JunB deletion can induce the transformation of low-thermogenic brown adipocytes into high-thermogenic brown adipocytes. Compared with the brown fat that normally expressed JunB, the proportion of high-thermogenic adipocytes in the brown fat depleted by JunB increased from 5.8% to 19.5%, and the proportion of low-thermogenic adipocytes decreased from 45.3% to 30.0%, and there was almost no difference in the proportion of medium-thermogenic adipocytes in the transitional state.
Mechanistically, JunB relies on the PGC-1α–ERRα pathway to regulate the thermogenesis of brown adipocytes. Specifically, PGC-1α needs to cooperate with estrogen-related receptor α (ERRα) to promote thermogenesis in adipocytes, but JunB, as a transcription factor, is able to inhibit the expression of EERα by binding to and acting on the promoter of ERRα, thereby interfering with the signaling pathway downstream of PGC-1α.
The proportion of brown adipocyte subsets changed after JunB knockout
When JunB of adipose tissue was specifically knocked out, the adipose thermogenesis capacity of mice was enhanced, the overall energy expenditure increased at room temperature, and the core body temperature was increased in low temperature environment, and the characteristics of brown fat with high thermogenesis were more obvious, which was manifested by an increase in the expression level of thermogenesis markers and an increase in the number of mitochondria-rich adipocytes.
Compared with wild-type mice, compared with wild-type mice, mice with adipose tissue-specific JunB had reduced body weight and fat mass gains, and improved insulin tolerance and hepatic steatosis.
Metabolism is improved in JunB-deficient mice
In conclusion, Meilian Liu et al. found that JunB plays a key role in regulating the thermogenesis of adipocytes, mediating the interconversion of hypothermic and hyperthermogenic adipocytes, and its expression levels in human neck fat correlate with body mass index.
In humans and rodents, brown fat has been shown to have a positive effect on cardiometabolic health and is an important area of research in the treatment of obesity and its related diseases. This study reveals that JunB may be a target to provide new insights into the treatment and intervention of obesity, inflammation and related diseases.
Quick, hurry up and get our brown fat that isn't rich to work!
Bibliography:
[1]https://www.nature.com/articles/s42255-023-00945-1
The author of this article丨Zhang Aidi