scholarly journals PRDM16 Represses the Pig White Lipogenesis through Promoting Lipolysis Activity

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Ting Gu ◽  
Guli Xu ◽  
Chengfeng Jiang ◽  
Lianjie Hou ◽  
Zhenfang Wu ◽  
...  
Keyword(s):  
Critical Role ◽  
Oxidative Capacity ◽  
Methyltransferase Activity ◽  
Newborn Piglets ◽  
White Adipocytes ◽  
Brown Adipose ◽  
Pr Domain ◽  
White Fat ◽  
Oil Red O Staining ◽  
Oil Red O

The positive regulatory domain containing 16 (PRDM16) gene is a dominant transcriptional regulator that favors the “browning” of white adipocytes in rodents. Since the “browning” of white fat is important in pig in terms of producing heat fighting against cold environment, avoiding obesity, and improving meat quality, understanding the critical role that PRDM16 gene played in pig adipose “browning” and energy metabolism is of great significance. However, the constitution of pig fat differs a lot from rodents and human as they do not have brown adipose tissue (BAT) even in the newborn piglets. In this study, we isolated porcine primary preadipocytes and investigated the function of PRDM16 during preadipocytes differentiation. Our results showed that overexpression of the PR domain of PRDM16 repressed the differentiation of porcine preadipocytes, indicated by oil red O staining and the deposition of the triglyceride. Overexpression of the PR domain significantly increased the level of lipolysis and mitochondrial oxidative capacity detected by Western blotting during differentiation. Furthermore, we purified the protein coded by the PR domain and demonstrated that this protein has the H3K9me1 methyltransferase activity. In conclusion, the PR domain of the porcine PRDM16 gene repressed the mature of the porcine preadipocytes by promoting its oxidative activity.

scholarly journals Dot1l interacts with Zc3h10 to activate Ucp1 and other thermogenic genes

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Danielle Yi ◽  
Hai P Nguyen ◽  
Jennie Dinh ◽  
Jose A Viscarra ◽  
Ying Xie ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Target Genes ◽  
Critical Role ◽  
Direct Interaction ◽  
Fat Cell ◽  
Methyltransferase Activity ◽  
Promoter Regions ◽  
Brown Adipose ◽  
Thermogenic Capacity

Brown adipose tissue is a metabolically beneficial organ capable of dissipating chemical energy into heat, thereby increasing energy expenditure. Here, we identify Dot1l, the only known H3K79 methyltransferase, as an interacting partner of Zc3h10 that transcriptionally activates the Ucp1 promoter and other BAT genes. Through a direct interaction, Dot1l is recruited by Zc3h10 to the promoter regions of thermogenic genes to function as a coactivator by methylating H3K79. We also show that Dot1l is induced during brown fat cell differentiation and by cold exposure and that Dot1l and its H3K79 methyltransferase activity is required for thermogenic gene program. Furthermore, we demonstrate that Dot1l ablation in mice using Ucp1-Cre prevents activation of Ucp1 and other target genes to reduce thermogenic capacity and energy expenditure, promoting adiposity. Hence, Dot1l plays a critical role in the thermogenic program and may present as a future target for obesity therapeutics.

scholarly journals Dot1L interacts with Zc3h10 to activate UCP1 and other thermogenic genes

2020 ◽  
Author(s):  
Danielle Yi ◽  
Hai P. Nguyen ◽  
Jennie Dinh ◽  
Jose A. Viscarra ◽  
Ying Xie ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Target Genes ◽  
Critical Role ◽  
Direct Interaction ◽  
Fat Cell ◽  
Methyltransferase Activity ◽  
Promoter Regions ◽  
Brown Adipose ◽  
Thermogenic Capacity

ABSTRACTBrown adipose tissue is a metabolically beneficial organ capable of dissipating chemical energy into heat, thereby increasing energy expenditure. Here, we identify Dot1L, the only known H3K79 methyltransferase, as an interacting partner of Zc3h10 that transcriptionally activates the UCP1 promoter and other BAT genes. Through a direct interaction, Dot1L is recruited by Zc3h10 to the promoter regions of thermogenic genes to function as a coactivator by methylating H3K79. We also show that Dot1L is induced during brown fat cell differentiation and by cold exposure and that Dot1L and its H3K79 methyltransferase activity is required for thermogenic gene program. Furthermore, we demonstrate that Dot1L ablation in mice using UCP1-Cre prevents activation of UCP1 and other target genes to reduce thermogenic capacity and energy expenditure, promoting adiposity. Hence, Dot1L plays a critical role in the thermogenic program and may present as a future target for obesity therapeutics.

scholarly journals miR17-92 cluster drives white adipose tissue browning

2020 ◽  
Vol 65 (3) ◽  
pp. 97-107
Author(s):  
Yuanyuan Huang ◽  
Hanlin Zhang ◽  
Meng Dong ◽  
Lei Zhang ◽  
Jun Lin ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Critical Role ◽  
Beneficial Effects ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
Beige Fat ◽  
And Function ◽  
White Fat

White adipose tissue (WAT) browning may have beneficial effects for treating metabolic syndrome. miRNA are important regulators of the differentiation, development, and function of brown and beige adipocytes. Here, we found that the cold-inducible miRNA17-92 cluster is enriched in brown adipose tissue (BAT) compared with WAT. Overexpression of the miR17-92 cluster in C3H10T1/2 cells, a mouse mesenchymal stem cell line, enhanced the thermogenic capacity of adipocytes. Furthermore, we observed a significant reduction in adiposity in adipose tissue-specific miR17-92 cluster transgenic (TG) mice. This finding is partly explained by dramatic increases in white fat browning and energy expenditure. Interestingly, the miR17-92 cluster stimulated WAT browning without altering BAT activity in mice. In addition, when we removed the intrascapular BAT (iBAT), the TG mice could maintain their body temperature well under cold exposure. At the molecular level, we found that the miR17-92 cluster targets Rb1, a beige cell repressor in WAT. The present study reveals a critical role for the miR17-92 cluster in regulating WAT browning. These results may be helpful for better understanding the function of beige fat, which could compensate for the lack of BAT in humans, and may open new avenues for combatting metabolic syndrome.

scholarly journals Appetite and energy balance signals from adipocytes

2006 ◽  
Vol 361 (1471) ◽  
pp. 1237-1249 ◽  
Author(s):  
Paul Trayhurn ◽  
Chen Bing
Keyword(s):  
Adipose Tissue ◽  
Energy Balance ◽  
Food Intake ◽  
White Adipose Tissue ◽  
Critical Role ◽  
The Other ◽  
White Adipocytes ◽  
Extensive Range ◽  
Genes Encoding ◽  
White Fat

Interest in the biology of white adipose tissue has risen markedly with the recent surge in obesity and its associated disorders. The tissue is no longer viewed simply as a vehicle for lipid storage; instead, it is recognized as a major endocrine and secretory organ. White adipocytes release a multiplicity of protein hormones, signals and factors, termed adipokines, with an extensive range of physiological actions. Foremost among these various adipokines is the cytokine-like hormone, leptin, which is synthesized predominantly in white fat. Leptin plays a critical role in the control of appetite and energy balance, with mutations in the genes encoding the hormone or its receptor leading to profound obesity in both rodents and man. Leptin regulates appetite primarily through an interaction with hypothalamic neuroendocrine pathways, inhibiting orexigenic peptides such as neuropeptide Y and orexin A, and stimulating anorexigenic peptides such as proopiomelanocortin. White fat also secretes several putative appetite-related adipokines, which include interleukin-6 and adiponectin, but whether these are indeed significant signals in the regulation of food intake has not been established. Through leptin and the other adipokines it is evident that adipose tissue communicates extensively with other organs and plays a pervasive role in metabolic homeostasis.

scholarly journals Acute cold-induced suppression of ob (obese) gene expression in white adipose tissue of mice: mediation by the sympathetic system

1995 ◽  
Vol 311 (3) ◽  
pp. 729-733 ◽  
Author(s):  
P Trayhurn ◽  
J S Duncan ◽  
D V Rayner
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
White Adipose Tissue ◽  
Critical Role ◽  
Sympathetic System ◽  
Obese Gene ◽  
Ob Gene ◽  
Brown Adipose ◽  
White Fat

The effect of acute exposure to cold on the expression of the ob (obese) gene, which encodes a protein that plays a critical role in the regulation of energy balance and body weight, has been examined in epididymal white adipose tissue of mice. Overnight (18 h) exposure of mice to a temperature of 4 degrees C led to the disappearance of ob mRNA in epididymal white fat, and subsequent studies showed that a cold-induced loss of ob mRNA could occur in as little as 2-4 h of exposure to 4 degrees C. When mice exposed to cold for 18 h were returned to the warm (24 degrees C), there was a rapid stimulation of the expression of the ob gene, the mRNA returning within 2.5 h. Administration of noradrenaline led to a reduction in the level of ob mRNA in mice maintained in the warm, while isoprenaline resulted in the disappearance of the mRNA; these changes in ob mRNA were paralleled by similar changes in lipoprotein lipase mRNA. In contrast to white fat, the level of lipoprotein lipase mRNA in brown adipose tissue was increased by noradrenaline and isoprenaline. It is concluded that there is a cold-induced suppression of ob gene expression in white adipose tissue of mice and that this is mediated primarily by the sympathetic system. The profound effect of cold on ob gene expression indicates that the ob system relates to energy expenditure, as well as to satiety.

Adipokines: inflammation and the pleiotropic role of white adipose tissue

2022 ◽  
Vol 127 (2) ◽  
pp. 161-164
Author(s):  
Paul Trayhurn
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Physiological Role ◽  
Storage Organ ◽  
Multiple Functions ◽  
White Adipocytes ◽  
Brown Adipose ◽  
Simple Lipid ◽  
White Fat

I had been working on the endocrine and signalling role of white adipose tissue (WAT) since 1994 following the identification of the ob (Lep) gene(1), this after some 15 years investigating the physiological role of brown adipose tissue. The ob gene, a mutation in which it is responsible for the profound obesity of ob/ob (Lepob/Lepob) mice, is expressed primarily in white adipocytes and encodes the pleiotropic hormone leptin. The discovery of this adipocyte hormone had wide-ranging implications, including that white fat has multiple functions that far transcend the traditional picture of a simple lipid storage organ.

scholarly journals Turning WAT into BAT: a review on regulators controlling the browning of white adipocytes

2013 ◽  
Vol 33 (5) ◽  
Author(s):  
Kinyui Alice Lo ◽  
Lei Sun
Keyword(s):  
Adipose Tissue ◽  
Energy Balance ◽  
Uncoupling Protein ◽  
Transcriptional Regulators ◽  
Peroxisome Proliferator ◽  
Uncoupling Protein 1 ◽  
Peroxisome Proliferator Activated Receptor ◽  
White Adipocytes ◽  
Brown Adipose ◽  
Pr Domain

Adipose tissue has a central role in the regulation of energy balance and homoeostasis. There are two main types of adipose tissue: WAT (white adipose tissue) and BAT (brown adipose tissue). WAT from certain depots, in response to appropriate stimuli, can undergo a process known as browning where it takes on characteristics of BAT, notably the induction of UCP1 (uncoupling protein 1) expression and the presence of multilocular lipid droplets and multiple mitochondria. How browning is regulated is an intense topic of investigation as it has the potential to tilt the energy balance from storage to expenditure, a strategy that holds promise to combat the growing epidemic of obesity and metabolic syndrome. This review focuses on the transcriptional regulators as well as various proteins and secreted mediators that have been shown to play a role in browning. Emphasis is on describing how many of these factors exert their effects by regulating the three main transcriptional regulators of classical BAT development, namely PRDM16 (PR domain containing 16), PPARγ (peroxisome proliferator-activated receptor γ) and PGC-1α (peroxisome proliferator-activated receptor γ coactivator 1α), which have been shown to be the key nodes in the regulation of inducible brown fat.

scholarly journals Through fat and thin – a journey with the adipose tissues

2020 ◽  
pp. 1-13 ◽  
Author(s):  
Paul Trayhurn
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Nutritional Regulation ◽  
Adipose Tissues ◽  
General Role ◽  
White Adipocytes ◽  
Nutrition Research ◽  
Brown Adipose ◽  
Inflammatory State ◽  
White Fat

The paper is based on the lecture that I gave on receiving the Nutrition Society's inaugural Gowland Hopkins Award for contributions to Cellular and Molecular Nutrition. It reviews studies on the adipose tissues, brown and white, conducted by the groups that I have led since entering nutrition research in 1975. The initial focus was on exploring metabolic factors that underpin the development of obesity using animal models. This resulted in an interest in non-shivering thermogenesis with brown adipose tissue being identified as the key effector of facultative heat production. Brown fat is less thermogenically active in various obese rodents, and major changes in activity are exhibited under physiological conditions such as lactation and fasting consistent with a general role for the tissue in nutritional energetics. My interests moved to white adipose tissue following the cloning of the Ob gene. Our initial contributions in this area included demonstrating nutritional regulation of Ob gene expression and circulating leptin levels, as well as a regulatory role for the sympathetic nervous system operating through β3-adrenoceptors. My interests subsequently evolved to a wider concern with the endocrine/signalling role of adipose tissue. Inflammation is a characteristic of white fat in obesity with the release of inflammation-related adipokines, and we proposed that hypoxia underlies this inflammatory state. O2-deprivation was shown to have substantial effects on gene expression and cellular function in white adipocytes. The hypoxia studies led to the proposition that O2 should be considered as a critical macronutrient.

scholarly journals Mouse white adipocytes and 3T3-L1 cells display an anomalous pattern of carnitine palmitoyltransferase (CPT) I isoform expression during differentiation: Inter-tissue and inter-species expression of CPT I and CPT II enzymes

1997 ◽  
Vol 327 (1) ◽  
pp. 225-231 ◽  
Author(s):  
Nicholas F. BROWN ◽  
Jennifer K. HILL ◽  
Victoria ESSER ◽  
James L. KIRKLAND ◽  
Barbara E. CORKEY ◽  
...  
Keyword(s):  
Carnitine Palmitoyltransferase ◽  
Cell Physiology ◽  
Kinetic Properties ◽  
Rat Tissues ◽  
Fat Cell ◽  
White Adipocytes ◽  
Brown Adipose ◽  
Cpt I ◽  
White Fat

The outer mitochondrial membrane enzyme carnitine palmitoyltransferase I (CPT I) represents the initial and regulated step in the β-oxidation of fatty acids. It exists in at least two isoforms, denoted L (liver) and M (muscle) types, with very different kinetic properties and sensitivities to malonyl-CoA. Here we have examined the relative expression of the CPT I isoforms in two different models of adipocyte differentiation and in a number of rat tissues. Adipocytes from mice, hamsters and humans were also evaluated. Primary monolayer cultures of undifferentiated rat preadipocytes expressed solely L-CPT I, but significant levels of M-CPT I emerged after only 3 days of differentiation in vitro; in the mature cell M-CPT I predominated. In sharp contrast, the murine 3T3-L1 preadipocyte expressed essentially exclusively L-CPT I, both in the undifferentiated state and throughout the differentiation process in vitro. This was also true of the mature mouse white fat cell. Fully developed adipocytes from the hamster and human behaved similarly to those of the rat. Thus the mouse white fat cell differs fundamentally from those of the other species examined in terms of its choice of a key regulatory enzyme in fatty acid metabolism. In contrast, brown adipose tissue from all three rodents displayed the same isoform profiles, each expressing overwhelmingly M-CPT I. Northern blot analysis of other rat tissues established L-CPT I as the dominant isoform not only in liver but also in kidney, lung, ovary, spleen, brain, intestine and pancreatic islets. In addition to its primacy in skeletal muscle, heart and fat, M-CPT I was also found to dominate in the testis. The same inter-tissue isoform pattern (with the exception of white fat) was found in the mouse. Taken together, the data bring to light an intriguing divergence between white adipocytes of the mouse and other mammalian species. They also raise a cautionary note that should be considered in the choice of animal model used in further studies of fat cell physiology.

Therapeutic effect of Prdx1 on NAFLD mice may be related to the activation of Nrf-2/HO-1 pathway

2020 ◽  
Vol 26 ◽  
Author(s):  
Ru-Xue Bai ◽  
Ying-Ying Xu ◽  
Yan-Ming Chen ◽  
Geng Qin ◽  
Hui-Fen Wang ◽  
...  
Keyword(s):  
Positive Staining ◽  
Wild Type ◽  
Mice Model ◽  
Alcoholic Fatty Liver ◽  
Liver Histopathology ◽  
Final Weight ◽  
Oil Red O Staining ◽  
Alcoholic Fatty Liver Disease ◽  
Oil Red O ◽  
Liver Tissues

Objective: To investigate the effect of peroxiredoxin1 (Prdx1) on the methionine-choline deficient (MCD)- induced mice model of non-alcoholic fatty liver disease (NAFLD). Methods: Wild type (WT), transgenic Prdx1 over-expressing (TG) and Prdx1 knockout (KO) mice were fed with MCD diet to construct NAFLD model. General parameters was determined followed by detection with HE staining, oil red O staining, Immunofluorescence, Immunohistochemistry, qRT-PCR and Western blotting. The activities of MDA, GPX and SOD were also quantified. Results: Compared with WT + MCD group, mice in KO + MCD group showed the decresed final weight, food intake and the levels of glucose, insulin, total cholesterol and triglyceride, accompanying with the increased FFA, ALT and AST, as well as the aggravated liver histopathology, which was alleviated in TG + MCD group. Also, mice from KO + MCD group had increased F4/80 and CD68 positive staining with the upregulation of pro-inflammatory and fibrogenic factors in liver tissues than those from WT + MCD group, as well as the enhanced MDA and the reduced GPX and SOD, while TG + MCD group demonstrated improvements than the WT + MCD group. Nrf-2/HO-1 pathway in liver tissues from NFALD mice was inhibited, and Prdx1-/- can further reduce the expression of Nrf-2 and HO-1, while Prdx1 overexpression increased Nrf-2 and HO-1 expression. Conclusion: Prdx1 improved oxidative stress, inflammation and fibrosis in liver of NAFLD mice, which may be associate with the activation of Nrf-2/HO-1 pathway.

Sign in / Sign up

Export Citation Format

Share Document