Studying Brown Adipose Tissue in a Human in vitro Context

Samuelson, Isabella; Vidal-Puig, António

doi:10.3389/fendo.2020.00629

Cited by 34 publications

(26 citation statements)

References 84 publications

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“…It is still difficult to isolate homogenous primary human beige (pre)adipocytes sporadically dispersed in white adipose depots. A proper model for human beige adipocytes has been required to identify small molecules and cytokines promoting brown adipogenesis 31 . Such bioactive molecules might have a therapeutic potential for the prevention of obesity and related metabolic diseases by controlling systemic energy balance.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis reveals brown adipogenic reprogramming in chemical compound-induced brown adipocytes converted from human dermal fibroblasts

Takeda

Yoshikawa

Dai

2021

Sci Rep

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Brown adipogenesis contributes to controlling systemic energy balance by enhancing glucose and lipid consumptions. We have previously reported chemical compound-induced brown adipocytes (ciBAs) directly converted from human dermal fibroblasts using a serum-free medium. In this study, genome-wide transcriptional analysis was performed in ciBAs in comparison with the control fibroblasts. A broad range of integrated gene expression was enhanced in functional groups including tricarboxylic acid cycle, electron transfer chain, triglycerides metabolism, fatty acid and glucose metabolism, and adaptive thermogenesis. The results suggested that the chemical conversion underwent metabolic and mitochondrial reprogramming closely associated with functions in brown/beige adipocytes. Moreover, we also compared the transcriptional changes to those of adipocyte browning in adipose tissue-derived mesenchymal stem cells (AdMSCs). Transcriptome analysis indicated that the same sets of metabolic and mitochondria-related genes were similarly changed in the adipocyte browning. Interestingly, ciBAs more expressed Ucp1, while AdMSC-derived adipocytes predominantly expressed Ucp2. UCP1 protein was also more expressed in ciBAs than in AdMSC-derived adipocytes. Based on the evidence that UCP1, but not UCP2, is responsible for adrenergic thermogenesis, ciBAs could be a promising model for human beige adipocytes applicable for basic research, drug development, and clinical uses.

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Section: Discussionmentioning

confidence: 99%

Transcriptome analysis reveals brown adipogenic reprogramming in chemical compound-induced brown adipocytes converted from human dermal fibroblasts

Takeda

Yoshikawa

Dai

2021

Sci Rep

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“…This is needed to reach to a robust conclusion on the impact of exercise on the browning process. Therefore, there have been recent calls for the development of more in vitro browning models, particularly involving cell-cell signaling [62]. In the present study, the co-culturing of two different cell types under the stimulus of EPS improved previous in vitro models for studying browning because it considers, for the first time, aspects of in vivo exercise physiology.…”

Section: Discussionmentioning

confidence: 92%

Effects of In Vitro Muscle Contraction on Thermogenic Protein Levels in Co-Cultured Adipocytes

Nintou

Karligiotou

Vliora

et al. 2021

Life

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The crosstalk between the exercising muscle and the adipose tissue, mediated by myokines and metabolites, derived from both tissues during exercise has created a controversy between animal and human studies with respect to the impact of exercise on the browning process. The aim of this study was to investigate whether co-culturing of C2C12 myotubes and 3T3-L1 adipocytes under the stimuli of electrical pulse stimulation (EPS) mimicking muscle contraction can impact the expression of UCP1, PGC-1a, and IL-6 in adipocytes, therefore providing evidence on the direct crosstalk between adipocytes and stimulated muscle cells. In the co-cultured C2C12 cells, EPS increased the expression of PGC-1a (p = 0.129; d = 0.73) and IL-6 (p = 0.09; d = 1.13) protein levels. When EPS was applied, we found that co-culturing led to increases in UCP1 (p = 0.044; d = 1.29) and IL-6 (p = 0.097; d = 1.13) protein expression in the 3T3-L1 adipocytes. The expression of PGC-1a increased by EPS but was not significantly elevated after co-culturing (p = 0.448; d = 0.08). In vitro co-culturing of C2C12 myotubes and 3T3-L1 adipocytes under the stimuli of EPS leads to increased expression of thermogenic proteins. These findings indicate changes in the expression pattern of proteins related to browning of adipose tissue, supporting the use of this in vitro model to study the crosstalk between adipocytes and contracting muscle.

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“…A fraction of adult humans can respond to cold stress by inducing the expression of thermogenic adipose tissue under relatively long-term cold acclimation in adult humans (McNeill, Suchacki et al 2021). However, it remains somewhat controversial if this inducible thermogenic human brown adipose tissue is the rodent equivalent of beige or brown adipocytes (Cannon, de Jong et al 2020, Samuelson and Vidal-Puig 2020, Virtanen and Nuutila 2021. In addition, whether the mass of the human inducible thermogenic adipocytes is sufficient to significantly contribute to cold responsive thermogenesis for core temperature maintenance or weight loss has also been questioned (Blondin, Tingelstad et al 2014, Virtanen andNuutila 2021).…”

Section: Discussionmentioning

confidence: 99%

TIGAR deficiency enhances skeletal muscle thermogenesis by increasing neuromuscular junction cholinergic signaling

Tang

Zong

Kwon

et al. 2022

eLife

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Cholinergic and sympathetic counter-regulatory networks control numerous physiologic functions including learning/memory/cognition, stress responsiveness, blood pressure, heart rate and energy balance. As neurons primarily utilize glucose as their primary metabolic energy source, we generated mice with increased glycolysis in cholinergic neurons by specific deletion of the fructose-2,6-phosphatase protein TIGAR. Steady-state and stable isotope flux analyses demonstrated increased rates of glycolysis, acetyl-CoA production, acetylcholine levels and density of neuromuscular synaptic junction clusters with enhanced acetylcholine release. The increase in cholinergic signaling reduced blood pressure and heart rate with a remarkable resistance to cold-induced hypothermia. These data directly demonstrate that increased cholinergic signaling through the modulation of glycolysis has several metabolic benefits particularly to increase energy expenditure and heat production upon cold exposure.

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Studying Brown Adipose Tissue in a Human in vitro Context

Cited by 34 publications

References 84 publications

Transcriptome analysis reveals brown adipogenic reprogramming in chemical compound-induced brown adipocytes converted from human dermal fibroblasts

Transcriptome analysis reveals brown adipogenic reprogramming in chemical compound-induced brown adipocytes converted from human dermal fibroblasts

Effects of In Vitro Muscle Contraction on Thermogenic Protein Levels in Co-Cultured Adipocytes

TIGAR deficiency enhances skeletal muscle thermogenesis by increasing neuromuscular junction cholinergic signaling

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