PPARγ and PPARα synergize to induce robust browning of white fat in vivo

Kroon, Tobias; Harms, Matthew; Maurer, Stefanie; Bonnet, L.; Alexandersson, Ida; Lindblom, Anna; Ahnmark, Andrea; Nilsson, Daniel; Gennemark, Peter; O’Mahony, Gavin; Osinski, Victoria; McNamara, Coleen A.; Boucher, Jérémie

doi:10.1016/j.molmet.2020.02.007

Cited by 52 publications

(42 citation statements)

References 63 publications

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“…We then induced white adipogenic differentiation in the presence of drugs to evaluate their browning/beiging effect. Rosiglitazone is a well-known browning agent [31,32]; as expected, it induced a strong upregulation of UCP1 and a significant decrease in C/EBPα, along with increased PPARγ levels (Figure 4). The FGF-21 did not modify either UCP1 or C/EBPα mRNA levels compared to the control: it induced an upregulation of LPL and C/EBPδ (Figure 4).…”

Section: Effect Of Browning Agents On White Adipogenesissupporting

confidence: 68%

Evaluation of Browning Agents on the White Adipogenesis of Bone Marrow Mesenchymal Stromal Cells: A Contribution to Fighting Obesity

Maio

Alessio

Demirsoy

et al. 2021

Cells

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Brown-like adipocytes can be induced in white fat depots by a different environmental or drug stimuli, known as “browning” or “beiging”. These brite adipocytes express thermogenin UCP1 protein and show different metabolic advantages, such as the ability to acquire a thermogenic phenotype corresponding to standard brown adipocytes that counteracts obesity. In this research, we evaluated the effects of several browning agents during white adipocyte differentiation of bone marrow-derived mesenchymal stromal cells (MSCs). Our in vitro findings identified two compounds that may warrant further in vivo investigation as possible anti-obesity drugs. We found that rosiglitazone and sildenafil are the most promising drug candidates for a browning treatment of obesity. These drugs are already available on the market for treating diabetes and erectile dysfunction, respectively. Thus, their off-label use may be contemplated, but it must be emphasized that some severe side effects are associated with use of these drugs.

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Section: Effect Of Browning Agents On White Adipogenesissupporting

confidence: 68%

Evaluation of Browning Agents on the White Adipogenesis of Bone Marrow Mesenchymal Stromal Cells: A Contribution to Fighting Obesity

Maio

Alessio

Demirsoy

et al. 2021

Cells

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“…Stimulation of PPARα or -γ induces browning in white adipocytes though PGC-1α-, UCP1- or SIRT-mediated pathways [ 22 , 25 , 57 ]. The PGC-1α protein is of key importance for the maintenance of insulin sensitivity and mitochondrial biogenesis in both hepatic and adipose tissues and its activation leads to browning through increase in UCP1 expression [ 18 , 24 , 29 , 58 ].…”

Section: Discussionmentioning

confidence: 99%

“…Another type of adipocytes—inducible brown-like adipocytes, localized in WAT—was described in recent decades and termed as beige or brown-in-white [ 14 , 16 , 19 , 22 , 23 ]. Cold exposure, β3-adrenergic agonist or prolonged peroxisome proliferator-activated receptor γ (PPARγ) agonist treatment, among other stimuli, trigger the biogenesis of beige adipocytes in WAT depots, also known as browning [ 6 , 17 , 23 , 24 , 25 ]. Like BAT, beige adipocytes expend energy in the form of heat, which has resulted in increased interest in the utilization of browning of white adipocytes as an option for cell-based therapy in obesity-related metabolic disorders [ 14 , 18 , 19 , 21 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

“…Like BAT, beige adipocytes expend energy in the form of heat, which has resulted in increased interest in the utilization of browning of white adipocytes as an option for cell-based therapy in obesity-related metabolic disorders [ 14 , 18 , 19 , 21 , 26 , 27 ]. Furthermore, pharmacological activation of the transition of white into beige adipocytes has been exploited as a promising approach for the drug-development of novel anti-obesity leads [ 19 , 22 , 25 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

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Caffeic and Chlorogenic Acids Synergistically Activate Browning Program in Human Adipocytes: Implications of AMPK- and PPAR-Mediated Pathways

Vasileva

Savova

Amirova

et al. 2020

IJMS

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Caffeic acid (CA) and chlorogenic acid (CGA) are phenolic compounds claimed to be responsible for the metabolic effects of coffee and tea consumption. Along with their structural similarities, they share common mechanisms such as activation of the AMP-activated protein kinase (AMPK) signaling. The present study aimed to investigate the anti-obesity potential of CA and CGA as co-treatment in human adipocytes. The molecular interactions of CA and CGA with key adipogenic transcription factors were simulated through an in silico molecular docking approach. The expression levels of white and brown adipocyte markers, as well as genes related to lipid metabolism, were analyzed by real-time quantitative PCR and Western blot analyses. Mechanistically, the CA/CGA combination induced lipolysis, upregulated AMPK and browning gene expression and downregulated peroxisome proliferator-activated receptor γ (PPARγ) at both transcriptional and protein levels. The gene expression profiles of the CA/CGA-co-treated adipocytes strongly resembled brown-like signatures. Major pathways identified included the AMPK- and PPAR-related signaling pathways. Collectively, these findings indicated that CA/CGA co-stimulation exerted a browning-inducing potential superior to that of either compound used alone which merits implementation in obesity management. Further, the obtained data provide additional insights on how CA and CGA modify adipocyte function, differentiation and lipid metabolism.

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“…Expression of PPAR β / δ has been shown to oscillate in-phase with that of UCP1 [ 178 ], suggesting that PPAR β / δ could regulate the circadian control of energy dissipation in BAT. PPARγ and PPARα synergize to induce browning of WAT in vivo, via PPARγ activation and PPARα-mediated FGF21 expression [ 180 ].…”

Section: Oxidative Stress and Circadian Rhythmmentioning

confidence: 99%

Circadian Rhythm in Adipose Tissue: Novel Antioxidant Target for Metabolic and Cardiovascular Diseases

Man¹,

Xia²,

Li³

2020

Antioxidants

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Obesity is a major risk factor for most metabolic and cardiovascular disorders. Adipose tissue is an important endocrine organ that modulates metabolic and cardiovascular health by secreting signaling molecules. Oxidative stress is a common mechanism associated with metabolic and cardiovascular complications including obesity, type 2 diabetes, and hypertension. Oxidative stress can cause adipose tissue dysfunction. Accumulating data from both humans and experimental animal models suggest that adipose tissue function and oxidative stress have an innate connection with the intrinsic biological clock. Circadian clock orchestrates biological processes in adjusting to daily environmental changes according to internal or external cues. Recent studies have identified the genes and molecular pathways exhibiting circadian expression patterns in adipose tissue. Disruption of the circadian rhythmicity has been suggested to augment oxidative stress and aberrate adipose tissue function and metabolism. Therefore, circadian machinery in the adipose tissue may be a novel therapeutic target for the prevention and treatment of metabolic and cardiovascular diseases. In this review, we summarize recent findings on circadian rhythm and oxidative stress in adipose tissue, dissect the key components that play a role in regulating the clock rhythm, oxidative stress and adipose tissue function, and discuss the potential use of antioxidant treatment on metabolic and cardiovascular diseases by targeting the adipose clock.

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PPARγ and PPARα synergize to induce robust browning of white fat in vivo

Cited by 52 publications

References 63 publications

Evaluation of Browning Agents on the White Adipogenesis of Bone Marrow Mesenchymal Stromal Cells: A Contribution to Fighting Obesity

Evaluation of Browning Agents on the White Adipogenesis of Bone Marrow Mesenchymal Stromal Cells: A Contribution to Fighting Obesity

Caffeic and Chlorogenic Acids Synergistically Activate Browning Program in Human Adipocytes: Implications of AMPK- and PPAR-Mediated Pathways

Circadian Rhythm in Adipose Tissue: Novel Antioxidant Target for Metabolic and Cardiovascular Diseases

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