Complex metabolic conditions such as type 2 diabetes and obesity result from the interaction of numerous genetic and environmental factors. While the family of Nme proteins has been connected so far mostly to development, proliferation, or ciliary functions, several lines of evidence from human and experimental studies point to the potential involvement of one of its members, NME7 (non-metastatic cells 7, nucleoside diphosphate kinase 7) in carbohydrate and lipid metabolism. As a complete lack of Nme7 is semilethal in rats, we compared morphometric, metabolic, and transcriptomic profiles of standard diet-fed heterozygous Nme7+/- on male rats vs. their wild-type Nme7+/+ controls. Nme7+/- animals showed increased body weight, adiposity, higher insulin levels together with decreased glucose tolerance. Moreover, they displayed pancreatic islet fibrosis and kidney tubular damage. Despite no signs of overt liver steatosis or dyslipidemia, we found significant changes in the hepatic transcriptome of Nme7+/- male rats with a concerted increase of expression of lipogenic enzymes including Scd1, Fads1, Dhcr7 and a decrease of Cyp7b1 and Nme7. Network analyses suggested possible links between Nme7 and the activation of Srebf1 and Srebf2 upstream regulators. These results further support the implication of NME7 in the pathogenesis of glucose intolerance and adiposity.

• Keywords
• animal models, metabolic syndrome, pancreatic fibrosis,
• MeSH
• Adiposity genetics   MeSH
• Diabetes Mellitus, Type 2 metabolism   MeSH
• Dyslipidemias genetics   MeSH
• Glucose metabolism   MeSH
• Liver metabolism   MeSH
• Rats MeSH
• Lipogenesis genetics   MeSH
• Lipid Metabolism physiology   MeSH
• Nucleoside-Diphosphate Kinase genetics   metabolism   MeSH
• Obesity metabolism   MeSH
• Glucose Intolerance genetics   metabolism   MeSH
• Rats, Sprague-Dawley MeSH
• Transcriptome MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Glucose MeSH
• NME7 protein, human MeSH Browser
• Nucleoside-Diphosphate Kinase MeSH

Ellagic acid, a natural substance found in various fruits and nuts, was previously shown to exhibit beneficial effects towards metabolic syndrome. In this study, using a genetic rat model of metabolic syndrome, we aimed to further specify metabolic and transcriptomic responses to ellagic acid treatment. Adult male rats of the SHR-Zbtb16Lx/k.o. strain were fed a high-fat diet accompanied by daily intragastric gavage of ellagic acid (50 mg/kg body weight; high-fat diet-ellagic acid (HFD-EA) rats) or vehicle only (high-fat diet-control (HFD-CTL) rats). Morphometric and metabolic parameters, along with transcriptomic profile of liver and brown and epididymal adipose tissues, were assessed. HFD-EA rats showed higher relative weight of brown adipose tissue (BAT) and decreased weight of epididymal adipose tissue, although no change in total body weight was observed. Glucose area under the curve, serum insulin, and cholesterol levels, as well as the level of oxidative stress, were significantly lower in HFD-EA rats. The most differentially expressed transcripts reflecting the shift induced by ellagic acid were detected in BAT, showing downregulation of BAT activation markers Dio2 and Nr4a1 and upregulation of insulin-sensitizing gene Pla2g2a. Ellagic acid may provide a useful nutritional supplement to ameliorate features of metabolic syndrome, possibly by suppressing oxidative stress and its effects on brown adipose tissue.

• Keywords
• brown adipose tissue, ellagic acid, insulin resistance, metabolic syndrome, oxidative stress,
• MeSH
• Biomarkers analysis   MeSH
• Diet, High-Fat MeSH
• Epididymis MeSH
• Adipose Tissue, Brown chemistry   MeSH
• Liver chemistry   MeSH
• Blood Glucose analysis   MeSH
• Rats MeSH
• Ellagic Acid administration & dosage   MeSH
• RNA, Messenger analysis   MeSH
• Metabolic Syndrome genetics   metabolism   prevention & control   MeSH
• Oxidative Stress drug effects   MeSH
• Rats, Inbred SHR MeSH
• RNA analysis   MeSH
• Transcriptome drug effects   MeSH
• Adipose Tissue chemistry   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Biomarkers MeSH
• Blood Glucose MeSH
• Ellagic Acid MeSH
• RNA, Messenger MeSH
• RNA MeSH