Berberine modulates deacetylation of PPARγ to promote adipose tissue remodeling and thermogenesis via AMPK/SIRT1 pathway

Xu, Yingxi; Yu, Tianhao; Ma, Guojing; Zheng, Lianfang; Jiang, Xuehan; Yang, Fan; Wang, Zhuo; Li, Na; He, Zheng; Song, Xiaoyu; Wen, Deliang; Kong, Juan; Yang, Yu; Cao, Liu

doi:10.7150/ijbs.62556

“…Berberine has been demonstrated as a chronic inflammation regulator as well [ 73 ]. A meta-analysis proved that berberine supplementation ameliorates the state of chronic inflammation by lowering the serum level of CRP [ 74 ]. Our meta-analysis illustrated that berberine significantly downregulates CRP, IL-6, and TNF- α .…”

Section: Discussionmentioning

confidence: 99%

The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

Guo

¹

,

Chen

²

,

Zhang

³

et al. 2021

Oxidative Medicine and Cellular Longevity

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Objective. Rhizoma Coptidis is an herb that has been frequently used in many traditional formulas for the treatment of diabetic mellitus (DM) over thousands of years. Berberine, the main active component of Rhizoma Coptidis, has been demonstrated to have the potential effect of hypoglycemia. To determine the potential advantages of berberine for diabetic care, we conducted this systematic review and meta-analysis to examine the efficacy and safety of berberine in the treatment of patients with type 2 DM. Methods. Eight databases including PubMed, Embase, Web of Science, the Cochrane library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database (SinoMed), Wanfang Database, and Chinese VIP Information was searched for randomized controlled trials (RCTs) reporting clinical data regarding the use of berberine for the treatment of DM. Publication qualities were also considered to augment the credibility of the evidence. Glycemic metabolisms were the main factors studied, including glycosylated hemoglobin (HbA1c), fasting plasm glucose (FPG), and 2-hour postprandial blood glucose (2hPG). Insulin resistance was estimated by fasting blood insulin (FINS), homeostasis model assessment-insulin resistance (HOMA-IR), and body mass index (BMI). Lipid profiles were also assessed, including triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), along with inflammation factors such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Serum creatinine (Scr), blood urea nitrogen (BUN), and adverse events were applied to evaluate the safety of berberine. Results. Forty-six trials were assessed. Analysis of berberine applied alone or with standard diabetic therapies versus the control group revealed significant reductions in HbA1c ( MD = − 0.73 ; 95% CI (−0.97, −0.51)), FPG ( MD = − 0.86 , 95% CI (−1.10, −0.62)), and 2hPG ( MD = − 1.26 , 95% CI (−1.64, −0.89)). Improved insulin resistance was assessed by lowering FINS ( MD = − 2.05 , 95% CI (−2.62, −1.48)), HOMA-IR ( MD = − 0.71 , 95% CI (−1.03, −0.39)), and BMI ( MD = − 1.07 , 95% CI (−1.76, −0.37)). Lipid metabolisms were also ameliorated via the reduction of TG ( MD = − 0.5 , 95% CI (−0.61, −0.39)), TC ( MD = 0.64 , 95% CI (−0.78, −0.49)), and LDL ( MD = 0.86 , 95% CI (−1.06, −0.65)) and the upregulation of HDL ( MD = 0.17 , 95% CI (0.09, 0.25)). Additionally, berberine improved the inflammation factor. Conclusion. There is strong evidence supporting the clinical efficacy and safety of berberine in the treatment of DM, especially as an adjunctive therapy. In the future, this may be used to guide targeted clinical use of berberine and the development of medications seeking to treat patients with T2DM and dyslipidemia.

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“…Tanshinone IIA, flavonoids extracted from mulberry leaves, and resveratrol all act by activating AMPK ( Zhang et al, 2019 ; Den Hartogh et al, 2020 ; Meng et al, 2020 ; Vlavcheski et al, 2020 ; Wen et al, 2020 ) ( Table 2 ). In addition, many natural products such as berberine and quercetin show great potential in regulating and activating the AMPK pathway ( Kjobsted et al, 2018 ; Wang N. et al, 2021 ; Xu et al, 2021 ). These studies suggest that plant-derived extracts can effectively activate the AMPK pathway and provide important information for the development of new drugs for many AMPK-related diseases.…”

Section: Adenosine Monophosphate Activated Protein Kinase and Its Act...mentioning

confidence: 99%

Adenosine monophosphate activated protein kinase contributes to skeletal muscle health through the control of mitochondrial function

Yan

¹

,

Li

²

,

Lin

³

et al. 2022

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Skeletal muscle is one of the largest organs in the body and the largest protein repository. Mitochondria are the main energy-producing organelles in cells and play an important role in skeletal muscle health and function. They participate in several biological processes related to skeletal muscle metabolism, growth, and regeneration. Adenosine monophosphate-activated protein kinase (AMPK) is a metabolic sensor and regulator of systemic energy balance. AMPK is involved in the control of energy metabolism by regulating many downstream targets. In this review, we propose that AMPK directly controls several facets of mitochondrial function, which in turn controls skeletal muscle metabolism and health. This review is divided into four parts. First, we summarize the properties of AMPK signal transduction and its upstream activators. Second, we discuss the role of mitochondria in myogenesis, muscle atrophy, regeneration post-injury of skeletal muscle cells. Third, we elaborate the effects of AMPK on mitochondrial biogenesis, fusion, fission and mitochondrial autophagy, and discuss how AMPK regulates the metabolism of skeletal muscle by regulating mitochondrial function. Finally, we discuss the effects of AMPK activators on muscle disease status. This review thus represents a foundation for understanding this biological process of mitochondrial dynamics regulated by AMPK in the metabolism of skeletal muscle. A better understanding of the role of AMPK on mitochondrial dynamic is essential to improve mitochondrial function, and hence promote skeletal muscle health and function.

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“…Plin5 not only regulates lipolysis directly on the surface of LDs but also acts as a transcriptional coactivator in response to catecholamine stimulation and participates in lipolysis. Mechanistically, catecholamine facilitates PKA phosphorylation of Plin5, leading to the translocation of Plin5 from LDs to the nucleus and the formation of transcriptional complexes with PGC-1α and silencing information regulator factor 2-related enzyme 1 (SIRT1) [73], which deacetylates PPARγ in a ligand-dependent manner [74,75]. Plin5 binds to SIRT1 and disinhibits its deacetylase activity, which in turn promotes PGC-1α promoter activity to activate PGC-1α target genes, thereby promoting the transcription of thermogenesis-related mitochondrial biogenesis, and oxidative function-related genes, ultimately leading to lipolysis [73].…”

Section: Lipid Droplet Proteins Regulate the Expression Of Thermogeni...mentioning

confidence: 99%

Lipid Droplets: A Cellular Organelle Vital for Thermogenesis

Chen¹,

Jin²,

Wu³

et al. 2022

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Mammals maintain a constant core body temperature through adaptive thermogenesis which includes shivering and non-shivering thermogenesis. Non-shivering thermogenesis relies primarily on mitochondrial uncoupling protein 1 (UCP1) in thermogenic fat (including brown and beige adipose tissue) to burn substrates, such as fatty acids (FAs), and convert chemical energy into heat. Lipid droplets (LDs), which are organelles that store lipids, are present in large numbers in thermogenic fat and are essential for adipose thermogenesis. Upon cold stimulation, LDs rapidly release FAs through autophagy or lipase-mediated lipolysis and rapidly translocate FAs into the mitochondria by interacting with mitochondria to burn and so promote thermogenesis. In addition, LD proteins promote the expression of UCP1 by activating the transcriptional activity of thermogenesis-related proteins. Here, the progress of research on the important role of LDs in thermogenesis is reviewed, mainly in terms of LD proteins, LD-organelle interactions, and LD autophagy (lipophagy). The emerging rationale for the involvement of LDs in each thermogenic pathway is described and the remaining unanswered questions in this field are highlighted.

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Berberine modulates deacetylation of PPARγ to promote adipose tissue remodeling and thermogenesis via AMPK/SIRT1 pathway

Cited by 42 publications

References 72 publications

The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

Adenosine monophosphate activated protein kinase contributes to skeletal muscle health through the control of mitochondrial function

Lipid Droplets: A Cellular Organelle Vital for Thermogenesis

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