1H NMR Metabolomics and Full-Length RNA-Seq Reveal Effects of Acylated and Nonacylated Anthocyanins on Hepatic Metabolites and Gene Expression in Zucker Diabetic Fatty Rats.

Kang Chen,Yumei Zhang,Baoru Yang,Maaria Kortesniemi,Xuetao Wei,Raghunath Pariyani

doi:10.1021/acs.jafc.1c00130

Kang Chen, Yumei Zhang + Show 4 more

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https://doi.org/10.1021/acs.jafc.1c00130

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Abstract

Anthocyanins have been reported to possess antidiabetic effects. Recent studies indicate acylated anthocyanins have better stability and antioxidative activity compared to their nonacylated counterparts. This study compared the effects of nonacylated and acylated anthocyanins on hepatic gene expression and metabolic profile in diabetic rats, using full-length transcriptomics and 1H NMR metabolomics. Zucker diabetic fatty (ZDF) rats were fed with nonacylated anthocyanin extract from bilberries (NAAB) or acylated anthocyanin extract from purple potatoes (AAPP) at daily doses of 25 and 50 mg/kg body weight for 8 weeks. Both anthocyanin extracts restored the levels of multiple metabolites (glucose, lactate, alanine, and pyruvate) and expression of genes (G6pac, Pck1, Pklr, and Gck) involved in glycolysis and gluconeogenesis. AAPP decreased the hepatic glutamine level. NAAB regulated the expression of Mgat4a, Gstm6, and Lpl, whereas AAPP modified the expression of Mgat4a, Jun, Fos, and Egr1. This study indicated different effects of AAPP and NAAB on the hepatic transcriptomic and metabolic profiles of diabetic rats.

Highlights

Anthocyanins, a major class of polyphenolic compounds in plants, are known to have a modulatory effect on oxidative stress, inflammation, and energy homeostasis.[1]
We found genes in MEgrey[60] and MEtan modules were significantly enriched in 20 KEGG pathways (Figure 7B), which were mainly involved in lipid metabolism, amino acid metabolism, diabetes, metabolic pathways, pyruvate metabolism, AMPactivated protein kinase phosphorylation (AMPK) signaling pathway, PPAR signaling pathway, and Th17 cell differentiation
Evidence has shown acylation of anthocyanins contributed differences in stability, antioxidant activity, and bioavailability between nonacylated and acylated anthocyanins; for example, acylated anthocyanins have been reported to have higher inhibitory activity on α-glucosidase than corresponding nonacylated anthocyanins;[25] acylated anthocyanins showed lower recovery in both urine and plasma compared to their nonacylated counterpart in a bioavailability study in humans, which indicates more acylated anthocyanins could be fermented by gut microbiota.[26]

Summary

Introduction

Anthocyanins, a major class of polyphenolic compounds in plants, are known to have a modulatory effect on oxidative stress, inflammation, and energy homeostasis.[1]. In our previous study using an NMR-metabolomics method, nonacylated and acylated anthocyanins displayed a different beneficial effect on the plasma metabolic profile of ZDF rats.[8] The liver plays a crucial role in the pathogenesis of T2D by regulating glucose metabolism and metabolic homeostasis.[9] We hypothesize that the anthocyanins regulate the hepatic metabolic profile by regulating the expression of the genes involved in energy metabolism in the liver; these changes can be revealed most efficiently by the powerful combination of high throughput methods of metabolomics and transcriptomics. We hypothesize that acylated anthocyanins and nonacylated anthocyanins have different effects on energy metabolism in the state of type 2 diabetes in vivo due to the difference in solubility, stability, and bioavailability

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