Trans-Cinnamic Acid Stimulates White Fat Browning and Activates Brown Adipocytes

Recently, pharmacological activation of brown fat and induction of white fat browning (beiging) have been considered promising strategies to treat obesity. To search for natural products that could stimulate the process of browning in adipocytes, we evaluated the activity of trans-cinnamic acid (tCA), a class of cinnamon from the bark of Cinnamomum cassia, by determining genetic expression using real time reverse transcription polymerase chain reaction (RT-PCR) and protein expression by immunoblot analysis for thermogenic and fat metabolizing markers. In our study tCA induced brown like-phenotype in 3T3-L1 white adipocytes and activated HIB1B brown adipocytes. tCA increased protein content of brown-fat-specific markers (UCP1, PRDM16, and PGC-1α) and expression levels of beige-fat-specific genes (Cd137, Cidea, Cited1, Tbx1, and Tmen26) in 3T3-L1 white adipocytes, as well as brown-fat-specific genes (Lhx8, Ppargc1, Prdm16, Ucp1, and Zic1) in HIB1B brown adipocytes. Furthermore, tCA reduced expression of key adipogenic transcription factors C/EBPα and PPARγ in white adipocytes, but enhanced their expressions in brown adipocytes. In addition, tCA upregulates lipid catabolism. Moreover, mechanistic study revealed that tCA induced browning in white adipocytes by activating the β3-AR and AMPK signaling pathways. tCA can induce browning, increase fat oxidation, reduce adipogenesis and lipogenesis in 3T3-L1 adipocytes, and activate HIB1B adipocytes, suggesting its potential to treat obesity.

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Betatrophin knockdown induces beiging and mitochondria biogenesis of white adipocytes

Journal of Endocrinology ◽

10.1530/joe-19-0447 ◽

2020 ◽

Vol 245 (1) ◽

pp. 93-100 ◽

Cited By ~ 1

Author(s):

Zhe-Zhen Liao ◽

Xiao-Yan Qi ◽

Ya-Di Wang ◽

Jiao-Yang Li ◽

Qian-Qian Gu ◽

...

Keyword(s):

Signaling Pathway ◽

Ampk Signaling ◽

White Adipocytes ◽

Beige Adipocytes ◽

Beige Fat ◽

Mitochondria Biogenesis ◽

Paracrine Actions ◽

White Fat

Remodeling of energy-storing white fat into energy-consuming beige fat has led to a promising new approach to alleviate adiposity. Several studies have shown adipokines can induce white adipose tissue (WAT) beiging through autocrine or paracrine actions. Betatrophin, a novel adipokine, has been linked to energy expenditure and lipolysis but not clearly clarified. Here, we using high-fat diet-induced obesity to determine how betatrophin modulate beiging and adiposity. We found that betatrophin-knockdown mice displayed less white fat mass and decreased plasma TG and NEFA levels. Consistently, inhibition of betatrophin leads to the phenotype change of adipocytes characterized by increased mitochondria contents, beige adipocytes and mitochondria biogenesis-specific markers both in vivo and in vitro. Of note, blocking AMP-activated protein kinase (AMPK) signaling pathway is able to abolish enhanced beige-like characteristics in betatrophin-knockdown adipocytes. Collectively, downregulation of betatrophin induces beiging in white adipocytes through activation of AMPK signaling pathway. These processes suggest betatrophin as a latent therapeutic target for obesity.

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Emergence during development of the white-adipocyte cell phenotype is independent of the brown-adipocyte cell phenotype

Biochemical Journal ◽

10.1042/bj3560659 ◽

2001 ◽

Vol 356 (2) ◽

pp. 659-664 ◽

Cited By ~ 21

Author(s):

Karine MOULIN ◽

Nathalie TRUEL ◽

Mireille ANDRÉ ◽

Emmanuelle ARNAULD ◽

Maryse NIBBELINK ◽

...

Keyword(s):

Brown Fat ◽

Late Gestation ◽

Brown Adipocyte ◽

Cell Phenotype ◽

Lacz Gene ◽

Experimental Proof ◽

Brown Adipocytes ◽

White Adipocytes ◽

Adipocyte Cell ◽

White Fat

In mammals, two types of adipose tissue are present, brown and white. They develop sequentially, as brown fat occurs during late gestation whereas white fat grows mainly after birth. However, both tissues have been shown to have great plasticity. Thus an apparent transformation of brown fat into white fat takes place during post-natal development. This observation raises questions about a possible conversion of brown into white adipocytes during development, although indirect data argue against this hypothesis. To investigate such questions in vivo, we generated two types of transgenic line. The first carried a transgene expressing Cre recombinase specifically in brown adipocytes under the control of the rat UCP1 promoter. The second corresponded to an inactive lacZ gene under the control of the human cytomegalovirus promoter. This dormant gene is inducible by Cre because it contains a Stop sequence between two loxP sequences, separating the promoter from the coding sequence. Adipose tissues of progeny derived by crossing independent lines established from both constructs were investigated. LacZ mRNA corresponding to the activated reporter gene was easily detected in brown fat and not typically in white fat, even by reverse transcriptase PCR experiments. These data represent the first direct experimental proof that, during normal development, most white adipocytes do not derive from brown adipocytes.

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Functional assessment of white and brown adipocyte development and energy metabolism in cell culture. Dissociation of terminal differentiation and thermogenesis in brown adipocytes

Journal of Cell Science ◽

10.1242/jcs.108.10.3171 ◽

1995 ◽

Vol 108 (10) ◽

pp. 3171-3180

Author(s):

S. Klaus ◽

M. Ely ◽

D. Encke ◽

G. Heldmaier

Keyword(s):

Uncoupling Protein ◽

Terminal Differentiation ◽

Brown Adipocyte ◽

Index Number ◽

Brown Adipocytes ◽

White Adipocytes ◽

Dwarf Hamster ◽

Microscopy Analysis ◽

White Fat ◽

Adipocyte Development

We investigated the effect of insulin, triiodothyronine (T3) and dexamethasone (a synthetic glucocorticoid) on differentiation, lipid metabolism and thermogenesis of preadipocytes isolated from white fat (WAT) and brown fat (BAT) from the Siberian dwarf hamster (Phodopus sungorus). Cell cultures from WAT and BAT were chronically treated with the above hormones alone or in any combination. After differentiation (day 8 or 9 of culture) we measured the following parameters: adipogenic index (number × size of adipocytes), protein content, lipolysis, cell respiration, and expression of the uncoupling protein UCP, which is unique to mitochondria of brown adipocytes. Insulin was the most important adipogenic factor for brown and white adipocytes and necessary for terminal differentiation, whereas dexamethasone alone completely inhibited differentiation. T3 had no effect on adipogenesis in WAT cultures, but further increased insulin stimulated adipogenesis in BAT cultures. Basal lipolysis was higher in WAT than in BAT cultures except when dexamethasone was present, which stimulated lipolysis in both culture types to the same extent. T3 had a pronounced dose dependent lipolytic effect on WAT cultures but very little effect on BAT cultures. Respiration rates were generally higher in differentiated adipocytes than in fibroblast like cells. T3 had no effect on thermogenesis in WAT cultures but increased thermogenesis in BAT cultures, and this was further elevated by insulin. UCP expression in BAT cultures could be detected by western blot in insulin treated, T3 treated and insulin+T3 treated cultures with highest expression in the latter. These results imply a possible dissociation of terminal differentiation and thermogenic function of brown adipocytes. In WAT cultures there was also a low level of UCP detectable in the insulin+T3 treated cultures. Immuno-fluorescence microscopy analysis revealed the presence of UCP in 10–15% of adipocytes from WAT cultures (in BAT cultures: 90%), indicating the presence of some brown preadipocytes in typical WAT deposits.

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Genetic variability affects the development of brown adipocytes in white fat but not in interscapular brown fat

The Journal of Lipid Research ◽

10.1194/jlr.m600287-jlr200 ◽

2006 ◽

Vol 48 (1) ◽

pp. 41-51 ◽

Cited By ~ 192

Author(s):

Bingzhong Xue ◽

Jong-Seop Rim ◽

Jessica C. Hogan ◽

Ann A. Coulter ◽

Robert A. Koza ◽

...

Keyword(s):

Genetic Variability ◽

Brown Fat ◽

Brown Adipocytes ◽

White Fat

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Brown and beige adipose tissues: phenotype and metabolic potential in mice and men

Journal of Applied Physiology ◽

10.1152/japplphysiol.00021.2017 ◽

2018 ◽

Vol 124 (2) ◽

pp. 482-496 ◽

Cited By ~ 11

Author(s):

Kanta Chechi ◽

Wouter van Marken Lichtenbelt ◽

Denis Richard

Keyword(s):

Brown Fat ◽

Whole Body ◽

Metabolic Potential ◽

Oxidative Potential ◽

Fat Depots ◽

Physiological Relevance ◽

Beige Fat ◽

Fat Stores ◽

White Fat ◽

Body Energy

With the recent rediscovery of brown fat in adult humans, our outlook on adipose tissue biology has undergone a paradigm shift. While we attempt to identify, recruit, and activate classic brown fat stores in humans, identification of beige fat has also raised the possibility of browning our white fat stores. Whether such transformation of human white fat depots can be achieved to enhance the whole body oxidative potential remains to be seen. Evidence to date, however, largely points toward a major oxidative role only for classic brown fat depots, at least in rodents. White fat stores seem to provide the main fuel for sustaining thermogenesis via lipolysis. Interestingly, molecular markers consistent with both classic brown and beige fat identity can be observed in human supraclavicular depot, thereby complicating the discussion on beige fat in humans. Here, we review the recent advances made in our understanding of brown and beige fat in humans and mice. We further provide an overview of their plausible physiological relevance to whole body energy metabolism.

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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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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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