Date of Completion

Spring 4-28-2015

Thesis Advisor(s)

Ji-Young Lee

Honors Major

Animal Science

Disciplines

Molecular, Genetic, and Biochemical Nutrition | Nutrition

Abstract

Hyperlipidemia and hyperglycemia frequently occur in obese population. As chronic, low-grade inflammation is closely associated with obesity, we investigated if polyphenol-rich blackcurrant extract (BCE) can prevent inflammation and diet-induced metabolic disturbances in mice. Male C57BL/6J mice were given a modified AIN-93M control diet containing high fat/high cholesterol (16% fat, 0.25% cholesterol by weight) or the same diet supplemented with 0.1% BCE (wt/wt) for 12 weeks. No significant differences in total body weight or liver weight occurred between the two groups. BCE-fed mice had fewer crown-like structures (CLS) with concomitant decreases in mRNA abundance of F4/80, CD68, and inhibitor of nuclear factor kB kinase e (IKKe) in the epididymal adipose tissue. F4/80 and IKKe mRNA levels were positively and significantly correlated with CLS number. BCE-fed mice demonstrated a significantly lower plasma total cholesterol (TC) and glucose levels than controls, but no significant difference in plasma triglyceride (TG) levels. BCE supplementation did not significantly alter mRNA levels of major regulators of hepatic cholesterol metabolism, i.e., HMG-CoA reductase (HMGR) and low density lipoprotein receptor (LDLR). However, protein expression levels of mature sterol-regulatory element binding protein 2 as well as LDLR were significantly increased. In the livers of mice fed BCE, there was a significant decrease in expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), which facilitates LDLR protein degradation, as well as one of its transcriptional regulators, i.e., hepatocyte nuclear factor 4 alpha. The skeletal muscle of BCE-fed mice showed a significant increase in mRNA expression of genes involved in energy expenditure and mitochondria biogenesis, including peroxisome proliferator activated receptor alpha (PPARalpha), PPARdelta, uncoupling protein 2 (UCP-2), UCP-3, and mitochondrial transcription factor A (TFAM). Upon stimulating splenocytes from BCE-fed mice with lipopolysaccharides, tumor necrosis factor alpha and interleukin-1beta mRNA levels were significantly lower than control mice (4). The results suggest that BCE supplementation decreases obesity-induced inflammation in adipose tissue and splenocytes, at least in part, by modulating energy metabolism in skeletal muscle. Beneficial effects of BCE on plasma TC and glucose, liver steatosis suggest that this berry may be consumed to prevent metabolic dysfunctions induced by diets high in fat and cholesterol.

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