scholarly journals Human beige adipocytes for drug discovery and cell therapy in metabolic diseases

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Amar M. Singh ◽  
Liang Zhang ◽  
John Avery ◽  
Amelia Yin ◽  
Yuhong Du ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Cell Therapy ◽  
Metabolic Diseases ◽  
Beige Adipocytes

scholarly journals Efficient differentiation of beige adipocytes from adult human adipose-derived stem/stromal cells

2020 ◽  
Author(s):  
Amar M. Singh ◽  
Liang Zhang ◽  
John Avery ◽  
Stephen Dalton
Keyword(s):  
Stem Cells ◽  
Cell Therapy ◽  
Drug Screening ◽  
Stromal Cells ◽  
High Efficiency ◽  
Disease Modelling ◽  
Serum Free ◽  
Beige Adipocytes ◽  
Free Media ◽  
Stromal Stem Cells

Abstract Beige adipocytes (also known as brite adipocytes) have significant utility for numerous applications, such as drug screening, cell therapy, and disease modelling. However, a high-efficiency protocol from human adult adipose-derived stem/stromal stem cells (ADSC) has not been described. The protocol described here achieves beige adipocyte purities of >92% in a fully-defined, serum-free media cocktail, which enables these downstream applications. This method provides a significant leap forward over previously described, serum-based protocols that were inconsistent and inefficient.

scholarly journals The Beige Adipocyte as a Therapy for Metabolic Diseases

2019 ◽  
Vol 20 (20) ◽  
pp. 5058 ◽  
Author(s):  
Fernando Lizcano
Keyword(s):  
Diabetes Mellitus ◽  
Adipose Tissue ◽  
Diabetes Mellitus Type 2 ◽  
Metabolic Diseases ◽  
Brown Fat ◽  
Diabetes Mellitus Type ◽  
Beige Adipocyte ◽  
Obesity And Diabetes ◽  
Beige Adipocytes

Adipose tissue is traditionally categorized into white and brown relating to their function and morphology. The classical white adipose tissue builds up energy in the form of triglycerides and is useful for preventing fatigue during periods of low caloric intake and the brown adipose tissue more energetically active, with a greater number of mitochondria and energy production in the form of heat. Since adult humans possess significant amounts of active brown fat depots and its mass inversely correlates with adiposity, brown fat might play an important role in human obesity and energy homeostasis. New evidence suggests two types of thermogenic adipocytes with distinct developmental and anatomical features: classical brown adipocytes and beige adipocytes. Beige adipocyte has recently attracted special interest because of its ability to dissipate energy and the possible ability to differentiate themselves from white adipocytes. The presence of brown and beige adipocyte in human adults has acquired attention as a possible therapeutic intervention for metabolic diseases. Importantly, adult human brown appears to be mainly composed of beige-like adipocytes, making this cell type an attractive therapeutic target for obesity and obesity-related diseases, such as atherosclerosis, arterial hypertension and diabetes mellitus type 2. Because many epigenetics changes can affect beige adipocyte differentiation from adipose progenitor cells, the knowledge of the circumstances that affect the development of beige adipocyte cells may be important to new pathways in the treatment of metabolic diseases. New molecules have emerged as possible therapeutic targets, which through the impulse to develop beige adipocytes can be useful for clinical studies. In this review will discuss some recent observations arising from the unique physiological capacity of these cells and their possible role as ways to treat obesity and diabetes mellitus type 2.

scholarly journals Scd1 controls de novo beige fat biogenesis through succinate-dependent regulation of mitochondrial complex II

2020 ◽  
Vol 117 (5) ◽  
pp. 2462-2472 ◽  
Author(s):  
Keli Liu ◽  
Liangyu Lin ◽  
Qing Li ◽  
Yueqing Xue ◽  
Fanjun Zheng ◽  
...  
Keyword(s):  
Cell Fate ◽  
Metabolic Diseases ◽  
De Novo ◽  
Great Promise ◽  
Mitochondrial Complex ◽  
Differentiation Potential ◽  
Complex Ii ◽  
White Adipocytes ◽  
Beige Adipocytes ◽  
Adipocyte Progenitors

Preadipocytes can give rise to either white adipocytes or beige adipocytes. Owing to their distinct abilities in nutrient storage and energy expenditure, strategies that specifically promote “beiging” of adipocytes hold great promise for counterbalancing obesity and metabolic diseases. Yet, factors dictating the differentiation fate of adipocyte progenitors remain to be elucidated. We found that stearoyl-coenzyme A desaturase 1 (Scd1)-deficient mice, which resist metabolic stress, possess augmentation in beige adipocytes under basal conditions. Deletion of Scd1 in mature adipocytes expressing Fabp4 or Ucp1 did not affect thermogenesis in mice. Rather, Scd1 deficiency shifted the differentiation fate of preadipocytes from white adipogenesis to beige adipogenesis. Such effects are dependent on succinate accumulation in adipocyte progenitors, which fuels mitochondrial complex II activity. Suppression of mitochondrial complex II by Atpenin A5 or oxaloacetic acid reverted the differentiation potential of Scd1-deficient preadipocytes to white adipocytes. Furthermore, supplementation of succinate was found to increase beige adipocyte differentiation both in vitro and in vivo. Our data reveal an unappreciated role of Scd1 in determining the cell fate of adipocyte progenitors through succinate-dependent regulation of mitochondrial complex II.

scholarly journals Identification of key candidate genes and molecular pathways in white fat browning: an anti-obesity drug discovery based on computational biology

2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Yuyan Pan ◽  
Jiaqi Liu ◽  
Fazhi Qi
Keyword(s):  
Adipose Tissue ◽  
Drug Discovery ◽  
Text Mining ◽  
Protein Interaction ◽  
Metabolic Diseases ◽  
Interaction Analysis ◽  
Brown Fat ◽  
Molecular Pathways ◽  
Protein Protein Interaction ◽  
White Fat

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.

scholarly journals Low-protein/high-carbohydrate diet induces AMPK-dependent canonical and non-canonical thermogenic response in subcutaneous adipose tissue

2020 ◽  
Author(s):  
Katia Aquilano ◽  
Francesca Sciarretta ◽  
Riccardo Turchi ◽  
Bo-Han Li ◽  
Marco Rosina ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Amino Acid ◽  
Metabolic Diseases ◽  
Metabolic Phenotype ◽  
Cool Temperature ◽  
Ampk Activation ◽  
Subcutaneous White Adipose Tissue ◽  
High Carbohydrate ◽  
Low Protein ◽  
Beige Adipocytes

ABSTRACTLow-protein/high-carbohydrate (LPHC) diet promotes metabolic health and longevity in adult humans and animal models. However, the complex molecular underpinnings of how LPHC diet leads to metabolic benefits remain elusive. Through a multi-layered approach, here we observed that LPHC diet promotes an energy-dissipating response consisting in the parallel recruitment of canonical and non-canonical (muscular) thermogenic systems in subcutaneous white adipose tissue (sWAT). In particular, we measured Ucp1 induction in association with up-regulation of actomyosin components and several Serca (Serca1, Serca2a, Serca2b) ATPases. In beige adipocytes, we observed that AMPK activation is responsible for transducing the amino acid lowering in an enhanced fat catabolism, which sustains both Ucp1- and Serca-dependent energy dissipation. Limiting AMPK activation counteracts the expression of brown fat and muscular genes, including Ucp1 and Serca, as well as mitochondrial oxidative genes. We observed that mitochondrial reactive oxygen species are the upstream molecules controlling AMPK-mediated metabolic rewiring in amino acid-restricted beige adipocytes. Our findings delineate a novel metabolic phenotype of responses to amino acid shortage, which recapitulates some of the benefits of cool temperature in sWAT. In conclusion, this highlights LPHC diet as a valuable and practicable strategy to prevent metabolic diseases through the enhancement of mitochondrial oxidative metabolism and the recruitment of different energy dissipating routes in beige adipocytes.

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