Transcription factor PU.1 is expressed in white adipose and inhibits adipocyte differentiation

Wang, Fei; Tong, Qiang

doi:10.1152/ajpcell.00422.2007

Cited by 58 publications

(65 citation statements)

References 51 publications

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“…Future work should concentrate on understanding the molecular mechanism through which ETS-5 controls body fat storage/metabolism through the action of neuropeptides, and how satiety signals control locomotion and feeding. Multiple ETS TFs have been linked to obesity in humans (57)(58)(59)(60), and thus the important role of the ETS-5 TF that we describe here may be conserved in higher organisms as well.…”

Section: Discussionmentioning

confidence: 83%

The ETS-5 transcription factor regulates activity states in Caenorhabditis elegans by controlling satiety

Juozaityte

Pladevall‐Morera

Podolska

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Animal behavior is shaped through interplay among genes, the environment, and previous experience. As in mammals, satiety signals induce quiescence in Caenorhabditis elegans. Here we report that the C. elegans transcription factor ETS-5, an ortholog of mammalian FEV/Pet1, controls satiety-induced quiescence. Nutritional status has a major influence on C. elegans behavior. When foraging, food availability controls behavioral state switching between active (roaming) and sedentary (dwelling) states; however, when provided with high-quality food, C. elegans become sated and enter quiescence. We show that ETS-5 acts to promote roaming and inhibit quiescence by setting the internal "satiety quotient" through fat regulation. Acting from the ASG and BAG sensory neurons, we show that ETS-5 functions in a complex network with serotonergic and neuropeptide signaling pathways to control food-regulated behavioral state switching. Taken together, our results identify a neuronal mechanism for controlling intestinal fat stores and organismal behavioral states in C. elegans, and establish a paradigm for the elucidation of obesity-relevant mechanisms.ETS transcription factor | neuronal signaling | satiety | fat levels | quiescence A nimal behavior is strongly influenced by the availability of food. In invertebrates and vertebrates, appetite, locomotor activity, and sleep rhythms are all driven by nutritional state (1-7). When malnourished, animals seek out a new food source by actively exploring their environment (roaming), whereas animals that are well fed tend to explore less (dwelling) and when fully sated enter a quiescent or sleep-like state (1-3, 8, 9). Transitions between these behavioral states can be regulated by sensory perception of external stimuli and through gut signals or other internal cues that are generated according to food quality (3,4,6).Initial evidence for neuronal regulation of feeding behavior was shown in mammals using hypothalamic lesions (10). Sectioning of specific regions within the rat hypothalamus evoked opposing behaviors. Removal of one section caused overeating and obesity, whereas removal of an adjacent section resulted in starvation owing to reduced eating (10). Subsequent studies showed that the pro-opiomelanocortin-expressing neurons in the hypothalamus function to suppress feeding, whereas a hypothalamic region that contains neuropeptide Y/agouti-related protein-expressing neurons promotes feeding (11). These adjacent brain regions integrate signals received from the gut that report satiety (12). The nutritive content of food itself also serves as a potent regulator of behavior. In mammals, a diet loaded with fats and sugars stimulates overfeeding and leads to obesity (13). In addition, rats can learn to select a source of food based exclusively on its nutritional value in the absence of external cues (14).In Caenorhabditis elegans, as in mammals, nutritive value is a behavioral stimulus (1, 4). Nematodes exhibit different behaviors when cultured on low-quality food compared to high-quality...

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Section: Discussionmentioning

confidence: 83%

The ETS-5 transcription factor regulates activity states in Caenorhabditis elegans by controlling satiety

Juozaityte

Pladevall‐Morera

Podolska

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…2A, compared with the control adipocytes expressing a scrambled shRNA, PU.1 shRNA-expressing adipocytes exhibit a 90% decreased PU.1 protein amount. Previously, we reported that overexpression of PU.1 suppresses adipogenesis (70). Here, downregulation of PU.1 expression enhanced adipocyte differentiation when the 3T3-L1 preadipocytes were differentiated under conventional conditions with exposure to a mixture of IBMX, dexamethasone, and insulin for 2 days and then insulin alone for another 4 days.…”

Section: Pu1 Is Expressed In the Adipocytes Of Obese Micementioning

confidence: 82%

“…Gonadal fat pads from A vy and lean control mice were minced in Krebs-Ringer phosphate buffer and digested with 1 mg/ml collagenase type I (Worthington Biochemical) at 37°C for 1 h, as described previously (70). Digested tissue was filtered through a nylon mesh and centrifuged at 500 rpm for 10 min.…”

Section: Methodsmentioning

confidence: 99%

“…We have reported that PU.1 expression in the adipose tissue is increased greatly in visceral fat of various obese mouse models (70). But the expression of PU.1 in different adipose depots in obese mice is unknown.…”

Section: Pu1 Is Expressed In the Adipocytes Of Obese Micementioning

confidence: 97%

“…Our recent study demonstrated that PU.1 is also expressed in adipocytes but not the stromal-vascular cells in the white adipose tissue (70). Similarly, PU.1 protein is not expressed in 3T3-L1 preadipocytes but is gradually upregulated at the late stage of adipocyte differentiation.…”

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confidence: 88%

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Adipocyte expression of PU.1 transcription factor causes insulin resistance through upregulation of inflammatory cytokine gene expression and ROS production

Lin

Pang

Chen

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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We have reported previously that ETS family transcription factor PU.1 is expressed in mature adipocytes of white adipose tissue. PU.1 expression is increased greatly in mouse models of genetic or diet-induced obesity. Here, we show that PU.1 expression is increased only in visceral but not subcutaneous adipose tissues of obese mice, and the adipocytes are responsible for this increase in PU.1 expression. To further address PU.1's physiological function in mature adipocytes, PU.1 was knocked down in 3T3-L1 cells using retroviral-mediated expression of PU.1-targeting shRNA. Consistent with previous findings that PU.1 regulates its target genes, such as NADPH oxidase subunits and proinflammatory cytokines in myeloid cells, the mRNA levels of proinflammatory cytokines (TNFα, IL-1β, and IL-6) and cytosolic components of NADPH oxidase (p47phox and p40phox) were downregulated significantly in PU.1-silenced adipocytes. NADPH oxidase is a main source for reactive oxygen species (ROS) generation. Indeed, silencing PU.1 suppressed NADPH oxidase activity and attenuated ROS in basal or hydrogen peroxide-treated adipocytes. Silencing PU.1 in adipocytes suppressed JNK1 activation and IRS-1 phosphorylation at Ser307. Consequently, PU.1 knockdown improved insulin signaling and increased glucose uptake in basal and insulin-stimulated conditions. Furthermore, knocking down PU.1 suppressed basal lipolysis but activated stimulated lipolysis. Collectively, these findings indicate that obesity induces PU.1 expression in adipocytes to upregulate the production of ROS and proinflammatory cytokines, both of which lead to JNK1 activation, insulin resistance, and dysregulation of lipolysis. Therefore, PU.1 might be a mediator for obesity-induced adipose inflammation and insulin resistance.

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CD9 Counteracts Liver Steatosis and Mediates GCGR Agonist Hepatic Effects

Zheng,

Wang,

Xiong

et al. 2024

Advanced Science

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Glucagon receptor (GCGR) agonism offers potentially greater effects on the mitigation of hepatic steatosis. However, its underlying mechanism is not fully understood. Here, it screened tetraspanin CD9 might medicate hepatic effects of GCGR agonist. CD9 is decreased in the fatty livers of patients and upregulated upon GCGR activation. Deficiency of CD9 in the liver exacerbated diet‐induced hepatic steatosis via complement factor D (CFD) regulated fatty acid metabolism. Specifically, CD9 modulated hepatic fatty acid synthesis and oxidation genes through regulating CFD expression via the ubiquitination‐proteasomal degradation of FLI1. In addition, CD9 influenced body weight by modulating lipogenesis and thermogenesis of adipose tissue through CFD. Moreover, CD9 reinforcement in the liver alleviated hepatic steatosis, and blockage of CD9 abolished the remission of hepatic steatosis induced by cotadutide treatment. Thus, CD9 medicates the hepatic beneficial effects of GCGR signaling, and may server as a promising therapeutic target for hepatic steatosis.

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Transcription factor PU.1 is expressed in white adipose and inhibits adipocyte differentiation

Cited by 58 publications

References 51 publications

The ETS-5 transcription factor regulates activity states in Caenorhabditis elegans by controlling satiety

The ETS-5 transcription factor regulates activity states in Caenorhabditis elegans by controlling satiety

Adipocyte expression of PU.1 transcription factor causes insulin resistance through upregulation of inflammatory cytokine gene expression and ROS production

CD9 Counteracts Liver Steatosis and Mediates GCGR Agonist Hepatic Effects

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