High fructose-induced skeletal muscle insulin resistance could be alleviated by berberine via AMPD1 and ADSL

Cheng, Juanjuan; Ma, Xingdong; Yan, Gaoliang; Yu, Qiuxia; Huang, Zhen; Lin, Guoshu; Li, Mengyao; Guan, Fengkun; Su, Ziren; Yan, Fang; Liu, Yuhong; Xie, Qingfeng

doi:10.1016/j.fct.2023.113731

Cited by 4 publications

(3 citation statements)

References 38 publications

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“…For example, BBR reduced the intracellular IR of hepatic cells induced by LTB4, 26 and BBR improved TNF‐α‐induced hepatic IR by targeting the MEKK1/MEK pathway 27 . In addition to the liver tissues, skeletal muscle, pancreas, and adipose tissues are also target organs of insulin, and BBR has been shown to improve high‐fructose‐induced IR in skeletal muscle 28 . However, the effects of BBR on obesity‐induced IR in mice, particularly its effects on skeletal muscle IR and pancreatic islets insulin secretion, have not been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

Berberine attenuates obesity‐induced insulin resistance by inhibiting miR‐27a secretion

Du,

Zhu,

Yang

et al. 2024

Diabet Med

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IntroductionBerberine (BBR) is an alkaloid found in plants. It has neuroprotective, anti‐inflammatory and lipid‐lowering activity. However, the efficacy of treatment with BBR and the mechanisms through which it acts need further study.AimsThis study investigated the therapeutic effects and the mechanism of action of BBR on obesity‐induced insulin resistance in peripheral tissues.MethodsHigh‐fat‐fed C57BL/6J mice and low‐fat‐fed C57BL/6J mice with miR‐27a overexpression were given BBR intervention (100 mg/kg, po), and the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed. Palmitic acid‐stimulated hypertrophic adipocyte models were treated with BBR (10 μM). Related indicators and protein expression levels were examined.ResultsThe AUCs of the OGTT and the ITT in the BBR intervention group were reduced significantly (p < 0.01) (p < 0.05), and the serum biochemical parameters, including FBG, TC, TG and LDL‐C were significantly reduced after BBR intervention. In the in vitro experiments, the triglyceride level and volume of lipid droplets decreased significantly after BBR intervention (p < 0.01) (p < 0.05). Likewise, BBR ameliorates skeletal muscle and pancreas insulin signalling pathways in vivo and in vitro.DiscussionThe results showed that BBR significantly ameliorated insulin resistance, reduced body weight and percent body fat and improved serum biochemical parameters in mice. Likewise, BBR reduced triglyceride level and lipid droplet volume in hypertrophic adipocytes, BBR improved obesity effectively. Meanwhile, BBR ameliorated the histomorphology of the pancreas, and skeletal muscle and pancreas insulin related signalling pathways of islets in in vitro and in vivo experiments. The results further demonstrated that BBR inhibited miR‐27a levels in serum from obese mice and supernatant of hypertrophic adipocytes. miR‐27a overexpression in low‐fat fed mice indicated that miR‐27a caused insulin resistance, and BBR intervention significantly improved the miR‐27a induced insulin resistance status.ConclusionThis study demonstrates the important role of BBR in obesity‐induced peripheral insulin resistance and suggest that the mechanism of its effect may be inhibition of miR‐27a secretion.

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Section: Discussionmentioning

confidence: 99%

Berberine attenuates obesity‐induced insulin resistance by inhibiting miR‐27a secretion

Du,

Zhu,

Yang

et al. 2024

Diabet Med

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“…Male mice were weighed from 21 days old until about 2 months old and dissected. Lee’s index = weight (g)^(1/3) x 10/body length (cm), where body length is defined as the distance from the nose to the anus ( Bernardis and Patterson, 1968 ; Cheng et al, 2023 ).…”

Section: Methodsmentioning

confidence: 99%

TRPC absence induces pro-inflammatory macrophage polarization to promote obesity and exacerbate colorectal cancer

Lin,

Gao,

Jing

et al. 2024

Front. Pharmacol.

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During the past half-century, although numerous interventions for obesity have arisen, the condition’s prevalence has relentlessly escalated annually. Obesity represents a substantial public health challenge, especially due to its robust correlation with co-morbidities, such as colorectal cancer (CRC), which often thrives in an inflammatory tumor milieu. Of note, individuals with obesity commonly present with calcium and vitamin D insufficiencies. Transient receptor potential canonical (TRPC) channels, a subclass within the broader TRP family, function as critical calcium transporters in calcium-mediated signaling pathways. However, the exact role of TRPC channels in both obesity and CRC pathogenesis remains poorly understood. This study set out to elucidate the part played by TRPC channels in obesity and CRC development using a mouse model lacking all seven TRPC proteins (TRPC HeptaKO mice). Relative to wild-type counterparts, TRPC HeptaKO mice manifested severe obesity, evidenced by significantly heightened body weights, augmented weights of epididymal white adipose tissue (eWAT) and inguinal white adipose tissue (iWAT), increased hepatic lipid deposition, and raised serum levels of total cholesterol (T-CHO) and low-density lipoprotein cholesterol (LDL-C). Moreover, TRPC deficiency was accompanied by an decrease in thermogenic molecules like PGC1-α and UCP1, alongside a upsurge in inflammatory factors within adipose tissue. Mechanistically, it was revealed that pro-inflammatory factors originating from inflammatory macrophages in adipose tissue triggered lipid accumulation and exacerbated obesity-related phenotypes. Intriguingly, considering the well-established connection between obesity and disrupted gut microbiota balance, substantial changes in the gut microbiota composition were detected in TRPC HeptaKO mice, contributing to CRC development. This study provides valuable insights into the role and underlying mechanisms of TRPC deficiency in obesity and its related complication, CRC. Our findings offer a theoretical foundation for the prevention of adverse effects associated with TRPC inhibitors, potentially leading to new therapeutic strategies for obesity and CRC prevention.

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“…By activating AMPK, BBR downregulated the expression of mTORC1/HIF-1α, thereby regulating the polarization of macrophages from the pro-inflammatory M1 type to the anti-inflammatory M2 type. This suppressed the glycolytic capacity of M1 macrophages, thus exerting an anti-arthritic effect ( Cheng et al, 2023 ). Notably, in rheumatoid arthritis, macrophages and T cells jointly mediate the inflammatory cascade response.…”

Section: Bbr Achieves Metabolic Regulation Through Important Target C...mentioning

confidence: 99%

Molecular mechanisms, targets and clinical potential of berberine in regulating metabolism: a review focussing on databases and molecular docking studies

Sun,

Yang,

et al. 2024

Front. Pharmacol.

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Background: Metabolic imbalance is the common basis of many diseases. As natural isoquinoline alkaloid, berberine (BBR) has shown great promise in regulating glucose and lipids metabolism and treating metabolic disorders. However, the related mechanism still lacks systematic research.Aim: To discuss the role of BBR in the whole body’s systemic metabolic regulation and further explore its therapeutic potential and targets.Method: Based on animal and cell experiments, the mechanism of BBR regulating systemic metabolic processes is reviewed. Potential metabolism-related targets were summarized using Therapeutic Target Database (TTD), DrugBank, GeneCards, and cutting-edge literature. Molecular modeling was applied to explore BBR binding to the potential targets.Results: BBR regulates the whole-body metabolic response including digestive, circulatory, immune, endocrine, and motor systems through adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), sirtuin (SIRT)1/forkhead box O (FOXO)1/sterol regulatory element-binding protein (SREBP)2, nuclear factor erythroid 2-related factor (Nrf) 2/heme oxygenase (HO)-1, and other signaling pathways. Through these reactions, BBR exerts hypoglycemic, lipid-regulating, anti-inflammatory, anti-oxidation, and immune regulation. Molecular docking results showed that BBR could regulate metabolism targeting FOXO3, Nrf2, NAD(P)H quinone oxidoreductase 1 (NQO1), glutathione peroxidase (Gpx) 4 and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Evaluating the target clinical effects, we found that BBR has the therapeutic potential of anti-aging, anti-cancer, relieving kidney disease, regulating the nervous system, and alleviating other chronic diseases.Conclusion: This review elucidates the interaction between potential targets and small molecular metabolites by exploring the mechanism of BBR regulating metabolism. That will help pharmacologists to identify new promising metabolites interacting with these targets.

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High fructose-induced skeletal muscle insulin resistance could be alleviated by berberine via AMPD1 and ADSL

Cited by 4 publications

References 38 publications

Berberine attenuates obesity‐induced insulin resistance by inhibiting miR‐27a secretion

Berberine attenuates obesity‐induced insulin resistance by inhibiting miR‐27a secretion

TRPC absence induces pro-inflammatory macrophage polarization to promote obesity and exacerbate colorectal cancer

Molecular mechanisms, targets and clinical potential of berberine in regulating metabolism: a review focussing on databases and molecular docking studies

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