Targeting mitochondrial quality control for diabetic cardiomyopathy: Therapeutic potential of hypoglycemic drugs

Zhou, Yutong; Suo, Wendong; Zhang, Xinai; Liang, Jiaojiao; Zhao, Weizhe; Wang, Yue; Li, Hong; Ni, Qing

doi:10.1016/j.biopha.2023.115669

Cited by 9 publications

(8 citation statements)

References 282 publications

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“…131 In people with T2D, metformin treatment decreases body weight by about 1.2-2.3% 133 and hyperglycemia along with reduction in risk of complications such as diabetic neuropathy and nephropathy and related cardiovascular outcomes. 134,135 In people with prediabetes, metformin treatment also reduces the risk of manifestation of T2D, but not necessarily cardiovascular outcomes. 98 Nevertheless, metformin treatment decreases body weight and hyperglycemia along with reduction in risk of microvascular and cardiovascular outcomes in people with overt T2D.…”

Section: Antihyperglycemic Drugsmentioning

confidence: 99%

“…Although the mechanisms of action are still under debate, complex I inhibition leading to AMPK activation, and more recently, alterations of the cellular redox balance likely explain the reduction of the excessive hepatic gluconeogenesis 131 . In people with T2D, metformin treatment decreases body weight by about 1.2–2.3% 133 and hyperglycemia along with reduction in risk of complications such as diabetic neuropathy and nephropathy and related cardiovascular outcomes 134,135 . In people with prediabetes, metformin treatment also reduces the risk of manifestation of T2D, but not necessarily cardiovascular outcomes 98 .…”

Section: Introductionmentioning

confidence: 99%

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Role of lifestyle and glucagon‐like peptide‐1 receptor agonists for weight loss in obesity, type 2 diabetes and steatotic liver diseases

Giannakogeorgou,

Roden

2024

Aliment Pharmacol Ther

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SummaryBackgroundThe current obesity pandemic has given rise to associated comorbidities and complications, including type 2 diabetes and metabolic dysfunction‐associated steatotic liver disease (MASLD). During the last decade, certain glucagon‐like peptide 1 receptor agonists (GLP‐1RA), originally developed as antihyperglycemic drugs, also demonstrated efficacy for weight loss.AimsTo review shared pathophysiologic features of common metabolic diseases and compare therapeutic strategies to reduce body weight and related complications.MethodsWe performed an extensive literature research to describe the effects of lifestyle modification, first‐generation anti‐obesity drugs, and GLP‐1RA on weight loss in humans with obesity, type 2 diabetes and MASLD.ResultsUntil recently, treatment of obesity has been limited to lifestyle modification, which offer moderate degree and sustainability of weight loss. The few approved first‐generation anti‐obesity drugs are either limited to short term use or to certain forms of obesity. Some GLP‐1RA significantly decrease caloric intake and body weight. Liraglutide and semaglutide have therefore been approved for treating people with obesity. They also lead to a reduction of hepatic fat content and inflammation in people with biopsy‐confirmed MASLD. Possible limitations comprise adverse effects, treatment adherence and persistence.ConclusionCertain GLP‐1RA are superior to lifestyle modification and first‐generation anti‐obesity drugs in inducing weight loss. They have therefore markedly changed the portfolio of obesity treatment with additional beneficial effects on steatotic liver disease.

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Section: Antihyperglycemic Drugsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of lifestyle and glucagon‐like peptide‐1 receptor agonists for weight loss in obesity, type 2 diabetes and steatotic liver diseases

Giannakogeorgou,

Roden

2024

Aliment Pharmacol Ther

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“…Mitochondria, the powerhouse of cells, require proper maintenance through processes like mitophagy, fusion, fission, and biogenesis to perform their physiological functions. However, in diabetic cardiomyopathy, there is a disruption in the quality control of mitochondria, which results in an inadequate fusion process, increased fission, and fragmentation [ 69 ]. Although only a small number of cardiomyocytes experience cell death due to apoptosis, activating apoptotic pathways can worsen cardiac dysfunction.…”

Section: Heart Failurementioning

confidence: 99%

Bridging the gap between GLP1-receptor agonists and cardiovascular outcomes: evidence for the role of tirzepatide

Taktaz,

Fontanella,

Scisciola

et al. 2024

Cardiovasc Diabetol

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Tirzepatide is a new drug targeting glucagon-like peptide 1(GLP1) and gastric inhibitory polypeptide (GIP) receptors. This drug has demonstrated great potential in improving the clinical outcomes of patients with type 2 diabetes. It can lead to weight loss, better glycemic control, and reduced cardiometabolic risk factors. GLP1 receptor agonists have been proven effective antidiabetic medications with possible cardiovascular benefits. Even though they have been proven to reduce the risk of major adverse cardiovascular events, their effectiveness in treating heart failure is unknown. Unlike traditional GLP1 receptor agonists, tirzepatide is more selective for the GIP receptor, resulting in a more balanced activation of these receptors. This review article discusses the possible mechanisms tirzepatide may use to improve cardiovascular health. That includes the anti-inflammatory effect, the ability to reduce cell death and promote autophagy, and also its indirect effects through blood pressure, obesity, and glucose/lipid metabolism. Additionally, tirzepatide may benefit atherosclerosis and lower the risk of major adverse cardiac events. Currently, clinical trials are underway to evaluate the safety and efficacy of tirzepatide in patients with heart failure. Overall, tirzepatide’s dual agonism of GLP1 and GIP receptors appears to provide encouraging cardiovascular benefits beyond glycemic control, offering a potential new therapeutic option for treating cardiovascular diseases and heart failure. Graphical abstract

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“…These mitochondrial regulations are known as mitochondrial quality control (MQC). Moreover, MQC is associated with a variety of diseases, such as aging ( Okatani et al, 2002 ; Zhang et al, 2023 ), cancers ( de Almeida Chuffa et al, 2019 ; Reiter et al, 2020a ; Zhang et al, 2023 ), cardiomyopathy ( Cai et al, 2022 ; Zhou et al, 2023 ), intestinal inflammation ( Motilva et al, 2011 ; Ma et al, 2020 ), ischemia/reperfusion injury ( Chen et al, 2016 ; Bai et al, 2023 ), liver disease ( Mauriz et al, 2007 ; Solís-Muñoz et al, 2011 ; Zhou et al, 2018a ), and neurodegenerative diseases ( Jauhari et al, 2020 ; Hossain et al, 2021 ; Austad et al, 2022 ; Xu et al, 2023 ; Han et al, 2023 ). Therefore, revealing the molecular mechanisms of MQC dysregulated may provide new prospects for therapeutic drug development in related diseases.…”

Section: Introductionmentioning

confidence: 99%

The potential influence of melatonin on mitochondrial quality control: a review

Lei,

Xu,

Huang

et al. 2024

Front. Pharmacol.

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Mitochondria are critical for cellular energetic metabolism, intracellular signaling orchestration and programmed death regulation. Therefore, mitochondrial dysfunction is associated with various pathogeneses. The maintenance of mitochondrial homeostasis and functional recovery after injury are coordinated by mitochondrial biogenesis, dynamics and autophagy, which are collectively referred to as mitochondrial quality control. There is increasing evidence that mitochondria are important targets for melatonin to exert protective effects under pathological conditions. Melatonin, an evolutionarily conserved tryptophan metabolite, can be synthesized, transported and metabolized in mitochondria. In this review, we summarize the important role of melatonin in the damaged mitochondria elimination and mitochondrial energy supply recovery by regulating mitochondrial quality control, which may provide new strategies for clinical treatment of mitochondria-related diseases.

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Targeting mitochondrial quality control for diabetic cardiomyopathy: Therapeutic potential of hypoglycemic drugs

Cited by 9 publications

References 282 publications

Role of lifestyle and glucagon‐like peptide‐1 receptor agonists for weight loss in obesity, type 2 diabetes and steatotic liver diseases

Role of lifestyle and glucagon‐like peptide‐1 receptor agonists for weight loss in obesity, type 2 diabetes and steatotic liver diseases

Bridging the gap between GLP1-receptor agonists and cardiovascular outcomes: evidence for the role of tirzepatide

The potential influence of melatonin on mitochondrial quality control: a review

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