Avatars of adipose tissue: the saga of transformation of white fat, the villain into brown fat, the protector. Focus on “Inflammation induced by RAW macrophages suppresses the UCP1 mRNA induction via ERK activation in 10T1/2 adipocytes”

Abstract Background Obesity—with its increased risk of obesity-associated metabolic diseases—has become one of the greatest public health epidemics of the twenty-first century in affluent countries. To date, there are no ideal drugs for treating obesity. Studies have shown that activation of brown adipose tissue (BAT) can promote energy consumption and inhibit obesity, which makes browning of white adipose tissue (WAT) a potential therapeutic target for obesity. Our objective was to identify genes and molecular pathways associated with WAT and the activation of BAT to WAT browning, by using publicly available data and computational tools; this knowledge might help in targeting relevant signaling pathways for treating obesity and other related metabolic diseases. Results In this study, we used text mining to find out genes related to brown fat and white fat browning. Combined with biological process and pathway analysis in GeneCodis and protein-protein interaction analysis by using STRING and Cytoscape, a list of high priority target genes was developed. The Human Protein Atlas was used to analyze protein expression. Candidate drugs were derived on the basis of the drug-gene interaction analysis of the final genes. Our study identified 18 genes representing 6 different pathways, targetable by a total of 33 drugs as possible drug treatments. The final list included 18 peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists, 4 beta 3 adrenoceptor (β3-AR) agonists, 1 insulin sensitizer, 3 insulins, 6 lipase clearing factor stimulants and other drugs. Conclusions Drug discovery using in silico text mining, pathway, and protein-protein interaction analysis tools may be a method of exploring drugs targeting the activation of brown fat or white fat browning, which provides a basis for the development of novel targeted therapies as potential treatments for obesity and related metabolic diseases.

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Reduction of dietary obesity in aP2-Ucp transgenic mice: mechanism and adipose tissue morphology

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1996.270.5.e776 ◽

1996 ◽

Vol 270 (5) ◽

pp. E776-E786 ◽

Cited By ~ 17

Author(s):

J. Kopecky ◽

M. Rossmeisl ◽

Z. Hodny ◽

I. Syrovy ◽

M. Horakova ◽

...

Keyword(s):

Adipose Tissue ◽

Transgenic Mice ◽

Cytochrome Oxidase ◽

Oxidase Activity ◽

Brown Fat ◽

Small Cells ◽

Cytochrome Oxidase Activity ◽

Tissue Morphology ◽

Brown Adipose ◽

White Fat

C57BL6/J mice with the expression of the mitochondrial uncoupling protein (UCP) gene from the fat-specific aP2 gene promoter were used to study the mechanism by which the aP2-Ucp transgene affects adiposity and reduces high-fat diet induced obesity. In the transgenic mice, UCP synthesized in white fat was inserted into mitochondria, and oxygen uptake by epididymal fat fragments indicated UCP-induced thermogenesis. The respirometry data, UCP content, cytochrome oxidase activity, and tissue morphology suggested functional involution of brown fat. Despite 25- to 50-fold lower mitochondrial cytochrome oxidase activity in white than in brown fat cells, total oxidative capacity in white and brown adipose tissue is comparable. Appearance of novel small cells in the gonadal fat of the transgenic mice was associated with a higher DNA content than that of the nontransgenic mice. The results prove a potential of transgenically altered mitochondria in white fat to modulate adiposity and energy expenditure and suggest the existence of a yet unidentified site-specific link between energy metabolism in adipocytes and cellularity.

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Identification of inducible brown adipocyte progenitors residing in skeletal muscle and white fat

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1010929108 ◽

2010 ◽

Vol 108 (1) ◽

pp. 143-148 ◽

Cited By ~ 314

Author(s):

Tim J. Schulz ◽

Tian Lian Huang ◽

Thien T. Tran ◽

Hongbin Zhang ◽

Kristy L. Townsend ◽

...

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

Cell Fate ◽

Brown Fat ◽

Brown Adipocyte ◽

Molecular Characteristics ◽

Fat Cell ◽

Interscapular Brown Adipose Tissue ◽

Brown Adipose ◽

White Fat

Brown fat is specialized for energy expenditure and has therefore been proposed to function as a defense against obesity. Despite recent advances in delineating the transcriptional regulation of brown adipocyte differentiation, cellular lineage specification and developmental cues specifying brown-fat cell fate remain poorly understood. In this study, we identify and isolate a subpopulation of adipogenic progenitors (Sca-1+/CD45−/Mac1−; referred to as Sca-1+ progenitor cells, ScaPCs) residing in murine brown fat, white fat, and skeletal muscle. ScaPCs derived from different tissues possess unique molecular expression signatures and adipogenic capacities. Importantly, although the ScaPCs from interscapular brown adipose tissue (BAT) are constitutively committed brown-fat progenitors, Sca-1+ cells from skeletal muscle and subcutaneous white fat are highly inducible to differentiate into brown-like adipocytes upon stimulation with bone morphogenetic protein 7 (BMP7). Consistent with these findings, human preadipocytes isolated from subcutaneous white fat also exhibit the greatest inducible capacity to become brown adipocytes compared with cells isolated from mesenteric or omental white fat. When muscle-resident ScaPCs are re-engrafted into skeletal muscle of syngeneic mice, BMP7-treated ScaPCs efficiently develop into adipose tissue with brown fat-specific characteristics. Importantly, ScaPCs from obesity-resistant mice exhibit markedly higher thermogenic capacity compared with cells isolated from obesity-prone mice. These data establish the molecular characteristics of tissue-resident adipose progenitors and demonstrate a dynamic interplay between these progenitors and inductive signals that act in concert to specify brown adipocyte development.

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Proses Pencokelatan Jaringan Adiposa

Indonesian Journal of Health Science ◽

10.54957/ijhs.v1i2.104 ◽

2021 ◽

Vol 1 (2) ◽

pp. 42-46

Author(s):

Afifa Radhina

Keyword(s):

Adipose Tissue ◽

Energy Consumption ◽

White Adipose Tissue ◽

Uncoupling Protein ◽

The Body ◽

Brown Fat ◽

Uncoupling Protein 1 ◽

Brown Adipocytes ◽

Major Health Problem ◽

White Fat

Obesity is a common, serious, and detrimental condition. In 2014, more than 1.9 billion adults were overweight. Obesity is associated with many diseases and the increase in obesity has become a major health problem. Obesity is caused by an imbalance between energy intake and energy consumption. Adipose tissue is an endocrine organ that secretes many hormones and cytokines that can affect metabolism. There are two types of adipose tissue in the body with different functions, namely white adipose tissue and brown adipose tissue. White fat has a major function in storing energy and is increased in obesity, while brown fat produces heat (thermogenesis) and then increases energy consumption. Therefore, brown fat and the induction of brown fat-like properties in white fat, have been considered as targets in the fight against obesity. The complex process of cell differentiation leading to the appearance of active brown adipocytes has been identified. There are classic brown adipocytes and cream adipocytes. Beige adipocytes are brown adipocytes that appear on precursor cells of white adipose tissue due to stimuli. Brown adipocytes are equipped with mitochondria containing uncoupling protein 1 (UCP1), which, when activated, controls ATP synthesis and stimulates respiratory chain activity. The browning process of adipose tissue is controlled by factors such as exercise. Obesitas merupakan keadaan yang umum, serius, dan merugikan. Tahun 2014, lebih dari 1,9 milyar orang dewasa mengalami kelebihan berat badan. Obesitas berasosiasi dengan banyak penyakit dan peningkatan obesitas telah menjadi masalah kesehatan utama. Obesitas disebabkan oleh ketidakseimbangan antara energi yang masuk dan konsumsi energi. Jaringan adiposa dalam tubuh ada dua tipe yang fungsinya berbeda, yakni jaringan adiposa putih dan jaringan adiposa cokelat. Lemak putih berfungsi utama dalam menyimpan energi dan meningkat pada obesitas, sedangkan lemak cokelat menghasilkan panas (termogenesis) dan kemudian meningkatkan konsumsi energi. Oleh karena itu, lemak cokelat dan induksi sifat seperti lemak cokelat pada lemak putih, telah dipertimbangkan sebagai target dalam melawan obesitas. Tujuan penelitian ini adalah untuk mengetahui proses pencoklatan jaringan adiposa putih. Metode penelitian yang digunakan adalah metode penelusuran ilmiah. Hasil penelitian diperoleh bahwa adiposit krem merupakan adiposit cokelat yang muncul pada sel prekursor dari jaringan adiposa putih karena adanya stimuli. Adiposit krem sama seperti adiposit cokelat dilengkapi dengan mitokondria yang mengandung uncoupling protein 1 (UCP1), yang ketika teraktivasi akan mengendalikan sintesis ATP dan menstimulasi aktivitas rantai respirasi. Beberapa regulator seperti PPAR γ, PGC-1α, dan PRDM16 muncul sebagai pelaku utama dalam proses diferensiasi adiposit krem.

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Brown Adipose YY1 Deficiency Activates Expression of Secreted Proteins Linked to Energy Expenditure and Prevents Diet-Induced Obesity

Molecular and Cellular Biology ◽

10.1128/mcb.00722-15 ◽

2015 ◽

pp. MCB.00722-15 ◽

Cited By ~ 4

Author(s):

Francisco Verdeguer ◽

Meghan S. Soustek ◽

Maximilian Hatting ◽

Sharon M. Blättler ◽

Devin McDonald ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Energy Expenditure ◽

Brown Adipose Tissue ◽

Brown Fat ◽

Secreted Proteins ◽

Fat Depots ◽

Diet Induced Obesity ◽

Brown Adipose ◽

White Fat

Mitochondrial oxidative and thermogenic function in brown and beige adipose tissues modulate rates of energy expenditure. It is unclear, however, how beige or white adipose tissue contributes to brown fat thermogenic function or compensate for partial deficiencies in this tissue and protect against obesity. Here, we show that the transcription factor YY1 in brown adipose tissue activates the canonical thermogenic and uncoupling gene expression program. In contrast, YY1 represses a series of secreted proteins including FGF21, BMP8b, GDF15, Angptl6, Neuromedin B and Nesfatin linked to energy expenditure. Despite substantial decreases in mitochondrial thermogenic proteins in brown fat, mice lacking YY1 in this tissue are strongly protected against diet-induced obesity, exhibit increased energy expenditure and oxygen consumption in beige and white fat depots. The increased expression of secreted proteins correlates with elevation of energy expenditure and promotion of beige and white fat activation. These results indicate that YY1 in brown adipose tissue controls antagonistic gene expression programs associated with energy balance and maintenance of body weight.

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Transcription Regulators and Hormones Involved in the Development of Brown Fat and White Fat Browning: Transcriptional and Hormonal Control of Brown/Beige Fat Development

Physiological Research ◽

10.33549/physiolres.933650 ◽

2018 ◽

pp. 347-362 ◽

Cited By ~ 7

Author(s):

J. ZHANG ◽

H. WU ◽

S. MA ◽

F. JING ◽

C. YU ◽

...

Keyword(s):

Adipose Tissue ◽

Hormonal Control ◽

Brown Fat ◽

Metabolic Complications ◽

Adipose Tissues ◽

Brown Adipose ◽

Beige Adipocytes ◽

New Strategy ◽

Beige Fat ◽

White Fat

The high prevalence of obesity and related metabolic complications has inspired research on adipose tissues. Three kinds of adipose tissues are identified in mammals: brown adipose tissue (BAT), beige or brite adipose tissue and white adipose tissue (WAT). Beige adipocytes share some characteristics with brown adipocytes such as the expression of UCP1. Beige adipocytes can be activated by environmental stimuli or pharmacological treatment, and this change is accompanied by an increase in energy consumption. This process is called white browning, and it facilitates the maintenance of a lean and healthy phenotype. Thus, promoting beige adipocyte development in WAT shows promise as a new strategy in treating obesity and related metabolic consequences. In this review, we summarized the current understanding of the regulators and hormones that participate in the development of brown fat and white fat browning.

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