Oral Spermidine Targets Brown Fat and Skeletal Muscle to Mitigate Diet‐Induced Obesity and Metabolic Disorders

Wang, Di; Yin, Jilong; Zhou, Zixin; Yan, Tao; Jia, Yufeng; Jie, Haipeng; Zhao, Jinshi; Li, Ruiyu; Li, Yuan; Guo, Chun; Zhu, Faliang; Mao, Hongzhi; Zhang, Lining; Wang, Qun

doi:10.1002/mnfr.202100315

Cited by 17 publications

(7 citation statements)

References 65 publications

(62 reference statements)

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“…Spermidine, as a natural polyamine that can be obtained from specific foods, has been found to play a key role in cell proliferation and is essential for the growth and development of children. Previous studies have suggested that spermidine supplementation may lead to varying degrees of improvement in weight status in high-fat diet-induced obese mice [17,18,20]. Moreover, an epidemiological study showed that spermidine intake was negatively associated with obesity [17].…”

Section: Discussionmentioning

confidence: 99%

“…Previous animal studies suggest that spermidine supplementation can help reduce body weight and improve metabolic disorders associated with obesity. In 2018, two animal studies consistently showed that spermidine supplementation caused a significant loss of weight and improved insulin resistance in high-fat diet-induced obese mice [17,18]. Furthermore, spermidine also can reduce the blood lipid level in high-fat diet-induced obese mice or acute hyperlipidemia mice [19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

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Elevation of Serum Spermidine in Obese Patients: Results from a Cross-Sectional and Follow-Up Study

Gao

Zhang

et al. 2022

Nutrients

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Background: Spermidine, a natural polyamine, appears to be a promising intervention for the treatment of obesity in animal studies, but epidemiological studies on the association between spermidine and obesity are inadequate. Methods: In the cross-sectional study, a total of 4230 eligible Chinese rural participants aged ≥ 35 years at baseline were recruited, of whom 1738 completed the two-year follow-up. Serum spermidines were measured using high-performance liquid chromatography with a fluorescence detector. Obesity and change in BMI were used as outcomes. Multivariable logistic regression analysis was applied to obtain the odds ratios (ORs) and 95% confidence intervals (CIs). Results: Participants who were obese had higher serum spermidine concentrations than those who were of normal weight (median (IQR), 27.2 ng/mL (14.8–53.4 ng/mL) vs. 23.8 ng/mL (12.8–46.6 ng/mL), p = 0.002). Compared with participants in the first quartile, those in the third quartile (OR 1.327, 95% CI 1.050 to 1.678) and the fourth quartile (OR 1.417, 95% CI 1.121 to 1.791) had a significantly increased risk of prevalent obesity after adjustment for confounding factors. In the follow-up study, participants in the third quartile (OR 0.712, 95% CI 0.535 to 0.946) and the fourth quartile (OR 0.493, 95% CI 0.370 to 0.657) had significantly lower risks of an increase in BMI after adjustment for confounding factors, with the lowest quartile as the reference. Meanwhile, we found a nonlinear relationship between spermidine and BMI in the follow-up study (p < 0.001). Conclusions: Serum spermidine was positively associated with increased odds of obesity in the cross-sectional study but reduced odds of an increase in BMI in the follow-up study among Chinese adults. Future studies are warranted to determine the exact mechanism underlying the association between spermidine and obesity and the scope for interventions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Elevation of Serum Spermidine in Obese Patients: Results from a Cross-Sectional and Follow-Up Study

Gao

Zhang

et al. 2022

Nutrients

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“…The study by Satish et al showed that mice with spermine treatment at a dose of 10 mg/kg resulted in a 24% reduction in body weight and an 18% reduction in fasting glucose [ 33 ]. Furthermore, as the decomposition product of spermine, spermidine has been well-known to be negatively correlated with lipid accumulation [ 37 , 38 ]. There are two pathways that convert spermine to spermidine ( Figure 6 B,C), including spermine oxidase which converts spermine into spermidine and 3-aminopropanal and acetylpolyamine oxidase, which converts spermine into spermidine and N-acetyl-1-spermine [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Using Untargeted LC-MS Metabolomics to Identify the Association of Biomarkers in Cattle Feces with Marbling Standard Longissimus Lumborum

Chen

et al. 2022

Animals

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Background: To improve the grade of beef marbling has great economic value in the cattle industry since marbling has the traits of high quality and comprehensive nutrition. And because of the marbling’s importance and complexity, it is indispensable to explore marbled beef at multiple levels. This experiment studied the relationship between fecal metabolites and marbling characters, and further screened biomarkers. Results: We performed fecal metabolomics analysis on 30 individuals selected from 100 crossbreed cattle (Luxi Yellow cattle ♀ × Japanese Wagyu cattle ♂), 15 with an extremely high-grade marbling beef and 15 with an extremely low-grade marbling beef. A total of 9959 and 8389 m/z features were detected in positive ionization and negative ionization mode by liquid chromatography-mass spectrometry (LC-MS). Unfortunately, the sample separation in the PCA is not obvious, and the predictive ability of the orthogonal partial least squares discrimination analysis (OPLS-DA) model is not good. However, we got six differential metabolites filtered by VIP > 1 and p < 0.05. After that, we used weighted correlation network analysis (WGCNA) and found out a module in each positive and negative mode most related to the trait of marbling beef, and then identified three metabolites in positive mode. By further annotation of the Kyoto encyclopedia of genes and genomes (KEGG), it was found that these metabolites involved a variety of metabolic ways, including sphingomyelin metabolism, linoleic acid metabolism, glycerophospholipid metabolism, and so on. Finally, receiver operating characteristic (ROC) analysis was used to evaluate the predictability of metabolites, and the result showed that SM(d18:0/16:1(9Z)) (AUC = 0.72), PC(15:0/18:2(9Z,12Z)) (AUC = 0.72), ADP (AUC = 0.71), PC(16:0/16:0) (AUC = 0.73), and 3-O-Sulfogalactosylceramide (d18:1/18:0) (AUC = 0.69) have an accuracy diagnosis. Conclusions: In conclusion, this study supports new opinions for the successive evaluation of marbling beef through metabolites. Furthermore, six non-invasive fecal metabolites that can evaluate beef marbling grade were found, including SM(d18:0/16:1(9Z)), PC(15:0/18:2(9Z,12Z)), ADP, PC(16:0/16:0), and 3-O-Sulfogalactosylceramide.

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“…While changes in circulating putrescine in NAFLD/NASH have not been reported yet and the evidence for decreased spermidine is limited ( 236 ), a number of studies reported a protective role of spermidine in mouse models of NAFLD. In diet-induced obese mice, supplementation with spermidine lowered hepatic steatosis associated with downregulation of lipogenic genes and upregulation of genes driving FAO, including Ppara ( 233 , 238 ). Also, spermidine ameliorated obesity-associated NAFLD in mice by increasing the phosphorylation of hepatic AMP-activated protein kinase (AMPK), which in turn inhibited the expression of the lipogenic genes Srebf1c and Fas ( 239 ).…”

Section: Emerging Biomarkers Linking Nafld/nash and Ascvd Offer Poten...mentioning

confidence: 99%

The interplay between nonalcoholic fatty liver disease and atherosclerotic cardiovascular disease

Finney

Das

Kumar

et al. 2023

Front. Cardiovasc. Med.

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Therapeutic approaches that lower circulating low-density lipoprotein (LDL)-cholesterol significantly reduced the burden of cardiovascular disease over the last decades. However, the persistent rise in the obesity epidemic is beginning to reverse this decline. Alongside obesity, the incidence of nonalcoholic fatty liver disease (NAFLD) has substantially increased in the last three decades. Currently, approximately one third of world population is affected by NAFLD. Notably, the presence of NAFLD and particularly its more severe form, nonalcoholic steatohepatitis (NASH), serves as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD), thus, raising interest in the relationship between these two diseases. Importantly, ASCVD is the major cause of death in patients with NASH independent of traditional risk factors. Nevertheless, the pathophysiology linking NAFLD/NASH with ASCVD remains poorly understood. While dyslipidemia is a common risk factor underlying both diseases, therapies that lower circulating LDL-cholesterol are largely ineffective against NASH. While there are no approved pharmacological therapies for NASH, some of the most advanced drug candidates exacerbate atherogenic dyslipidemia, raising concerns regarding their adverse cardiovascular consequences. In this review, we address current gaps in our understanding of the mechanisms linking NAFLD/NASH and ASCVD, explore strategies to simultaneously model these diseases, evaluate emerging biomarkers that may be useful to diagnose the presence of both diseases, and discuss investigational approaches and ongoing clinical trials that potentially target both diseases.

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Oral Spermidine Targets Brown Fat and Skeletal Muscle to Mitigate Diet‐Induced Obesity and Metabolic Disorders

Cited by 17 publications

References 65 publications

Elevation of Serum Spermidine in Obese Patients: Results from a Cross-Sectional and Follow-Up Study

Elevation of Serum Spermidine in Obese Patients: Results from a Cross-Sectional and Follow-Up Study

Using Untargeted LC-MS Metabolomics to Identify the Association of Biomarkers in Cattle Feces with Marbling Standard Longissimus Lumborum

The interplay between nonalcoholic fatty liver disease and atherosclerotic cardiovascular disease

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