Spermidine ameliorates non-alcoholic fatty liver disease through regulating lipid metabolism via AMPK

Gao, Mingyue; Zhao, Wei; Li, Chunmei; Xie, Xianghong; Li, Meixia; Bi, Yalan; Fang, Fude; Du, Yunfeng; Liu, Xiaojun

doi:10.1016/j.bbrc.2018.09.078

Cited by 50 publications

(45 citation statements)

References 38 publications

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“…In diet-induced obesity mouse models, a high-dose daily administration of either spermidine or spermine has been shown to be an effective strategy for weight loss and improvement of the glycemic status (103, 160, 161). For instance, spermidine supplementation resulted in a significant decrease in body weight, increased glucose tolerance and insulin sensitivity and ameliorated hepatic steatosis in high-fat diet-induced obese mice (161).…”

Section: Polyamines In Obesity and Related Metabolic Disordersmentioning

confidence: 99%

Dietary and Gut Microbiota Polyamines in Obesity- and Age-Related Diseases

et al. 2019

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The polyamines putrescine, spermidine, and spermine are widely distributed polycationic compounds essential for cellular functions. Intracellular polyamine pools are tightly regulated by a complex regulatory mechanism involving de novo biosynthesis, catabolism, and transport across the plasma membrane. In mammals, both the production of polyamines and their uptake from the extracellular space are controlled by a set of proteins named antizymes and antizyme inhibitors. Dysregulation of polyamine levels has been implicated in a variety of human pathologies, especially cancer. Additionally, decreases in the intracellular and circulating polyamine levels during aging have been reported. The differences in the polyamine content existing among tissues are mainly due to the endogenous polyamine metabolism. In addition, a part of the tissue polyamines has its origin in the diet or their production by the intestinal microbiome. Emerging evidence has suggested that exogenous polyamines (either orally administrated or synthetized by the gut microbiota) are able to induce longevity in mice, and that spermidine supplementation exerts cardioprotective effects in animal models. Furthermore, the administration of either spermidine or spermine has been shown to be effective for improving glucose homeostasis and insulin sensitivity and reducing adiposity and hepatic fat accumulation in diet-induced obesity mouse models. The exogenous addition of agmatine, a cationic molecule produced through arginine decarboxylation by bacteria and plants, also exerts significant effects on glucose metabolism in obese models, as well as cardioprotective effects. In this review, we will discuss some aspects of polyamine metabolism and transport, how diet can affect circulating and local polyamine levels, and how the modulation of either polyamine intake or polyamine production by gut microbiota can be used for potential therapeutic purposes.

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Section: Polyamines In Obesity and Related Metabolic Disordersmentioning

confidence: 99%

Dietary and Gut Microbiota Polyamines in Obesity- and Age-Related Diseases

et al. 2019

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“…Spermidine, a precursor to polyamines, has been shown to exert anti-inflammatory properties, and to inhibit age-related oxidative protein damage and ROS. To target lipid metabolism, spermidine induces AMPK pathway to regulate autophagy, in turn inhibiting expression of fatty acids (Gao et al, 2018).…”

Section: Dyslipidemiamentioning

confidence: 99%

The Vascular Consequences of Metabolic Syndrome: Rodent Models, Endothelial Dysfunction, and Current Therapies

et al. 2020

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Metabolic syndrome is characterized by visceral obesity, dyslipidemia, hyperglycemia and hypertension, and affects over one billion people. Independently, the components of metabolic syndrome each have the potential to affect the endothelium to cause vascular dysfunction and disrupt vascular homeostasis. Rodent models of metabolic syndrome have significantly advanced our understanding of this multifactorial condition. In this minireview we compare the currently available rodent models of metabolic syndrome and consider their limitations. We also discuss the numerous mechanisms by which metabolic abnormalities cause endothelial dysfunction and highlight some common pathophysiologies including reduced nitric oxide production, increased reactive oxygen species and increased production of vasoconstrictors. Additionally, we explore some of the current therapeutics for the comorbidities of metabolic syndrome and consider how these benefit the vasculature.

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“…Remarkably, polyamine metabolism has been directly implicated in adipogenesis [20,21,22], suggesting that increased polyamine levels might be involved in adipose tissue expansion in obesity. In diet-induced obesity mouse models, a high-dose daily administration of either spermidine or spermine has been shown to be an effective strategy for weight loss and improvement of glycemic status [23,24,25], indicating a possible therapeutic role for exogenous polyamines in metabolic disorders. In addition, emerging evidence has suggested a beneficial effect of chronic low-dose oral spermidine administration on cardiovascular disease in hypertensive experimental models [26].…”

Section: Introductionmentioning

confidence: 99%

Type 2 Diabetes Is Associated with a Different Pattern of Serum Polyamines: A Case–Control Study from the PREDIMED-Plus Trial

Fernández‐García

Delpino-Rius

Samarra

et al. 2019

JCM

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Objective: Polyamines are naturally occurring cationic molecules present in all living cells. Dysregulation of circulating polyamines has been reported in several conditions, but little is known about the levels of serum polyamines in chronic metabolic disorders such as type 2 diabetes (T2D). Therefore, the aim of this study was to evaluate the polyamine-related metabolome in a cohort of metabolic syndrome individuals with and without T2D. Design and methods: This was a nested case–control study within the PREDIMED-Plus trial that included 44 patients with T2D and 70 patients without T2D. We measured serum levels of arginine, ornithine, polyamines, and acetyl polyamines with an ultra-high performance liquid chromatography tandem mass spectrometry platform. Results: Our results showed that serum putrescine, directly generated from ornithine by the catalytic action of the biosynthetic enzyme ornithine decarboxylase, was significantly elevated in patients with T2D compared to those without T2D, and that it significantly correlated with the levels of glycosylated hemoglobin (HbA1c). Correlation analysis revealed a significantly positive association between fasting insulin levels and spermine. Multiple logistic regression analysis (adjusted for age, gender and body weight index) revealed that serum putrescine and spermine levels were associated with a higher risk of T2D. Conclusions: Our study suggests that polyamine metabolism is dysregulated in T2D, and that serum levels of putrescine and spermine are associated with glycemic control and circulating insulin levels, respectively.

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Spermidine ameliorates non-alcoholic fatty liver disease through regulating lipid metabolism via AMPK

Cited by 50 publications

References 38 publications

Dietary and Gut Microbiota Polyamines in Obesity- and Age-Related Diseases

Dietary and Gut Microbiota Polyamines in Obesity- and Age-Related Diseases

The Vascular Consequences of Metabolic Syndrome: Rodent Models, Endothelial Dysfunction, and Current Therapies

Type 2 Diabetes Is Associated with a Different Pattern of Serum Polyamines: A Case–Control Study from the PREDIMED-Plus Trial

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