Understanding the fiber-type specification and metabolic switch in skeletal muscle provides insights into energy metabolism in physiology and diseases. Here, we show that miR-182 is highly expressed in fast-twitch muscle and negatively correlates with blood glucose level. miR-182 knockout mice display muscle loss, fast-to-slow fiber-type switching, and impaired glucose metabolism. Mechanistic studies reveal that miR-182 modulates glucose utilization in muscle by targeting FoxO1 and PDK4, which control fuel selection via the pyruvate dehydrogenase complex (PDHC). Short-term high-fat diet (HFD) feeding reduces muscle miR-182 levels by tumor necrosis factor α (TNFα), which contributes to the upregulation of FoxO1/PDK4. Restoration of miR-182 expression in HFD-fed mice induces a faster muscle phenotype, decreases muscle FoxO1/PDK4 levels, and improves glucose metabolism. Together, our work establishes miR-182 as a critical regulator that confers robust and precise controls on fuel usage and glucose homeostasis. Our study suggests that a metabolic shift toward a faster and more glycolytic phenotype is beneficial for glucose control.

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Cytochrome P450 4F2 (CYP4F2) catalyzes the -hydroxylation of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a natriuretic and vasoactive eicosanoid that participates in the development of hypertension. The relationship among CYP4F2 genetic variants in the regulatory region, formation of renal 20-HETE, and hypertension is unknown. Here are reported seven genetic variants around the CYP4F2 intronic regulatory region. Four of these variants made up two common haplotypes, Hap I (c.Ϫ91T/c.Ϫ48G/c.Ϫ13T/c.ϩ34T) and Hap II (c.Ϫ91C/c.Ϫ48C/c.Ϫ13C/c.ϩ34G). Hap I included a major functional variant, c.Ϫ91T3 C, which was identified by reporter assay and electrophoretic mobility shift assay. Transfected into HEK293 cells, the Hap I construct showed a trend toward higher basal transcriptional activity and exhibited significantly greater LPS-stimulated activity than Hap II; these findings were the result of different NF-B binding affinity between the two constructs. In vivo, a case-control study demonstrated that homozygosity for Hap I doubled the risk for hypertension in a Chinese population, even after adjustment for risk factors including age, gender, and body mass index. This association was confirmed in a family-based association study. In addition, Hap I was associated with elevated urinary 20-HETE. These results indicate that a functional variant of the CYP4F2 regulatory region, which increases the binding affinity of NF-B, increases the risk for hypertension, likely by modulating the production of 20-HETE. The cytochrome P450 4F2 (CYP4F2) gene, prominently expressed in human kidney and liver, encodes an -hydroxylase that catalyzes the metabolism of arachidonic acid, 1 leukotriene B4, 2 and tocopherol. 3 The 20-hydroxyeicosatetraenoic acid (20-HETE), derived from arachidonic acid by CYP4F2 in the kidney, acts as a natriuretic and vasoactive eicosanoid and plays an important role in the control of renal function and systemic BP. 4,5 Considerable evidence showed that altered renal 20-HETE content and CYP genes were related to hypertension in animal models and in humans 6-10 ; however, the contribution of haplotypes in the CYP4F2 regulatory regiontorenal20-HETEexcretionaswellashumanhypertension remains unclear, because recent investigations indicated that the primary target variants for disease-gene association studies would be located in regulatory regions. 11 Hypertension is a common disease and an independent risk factor for stroke, heart failure, and ESRD. It is widely known that hypertension is a multifactorial disease whereby genetic determinants interact with environmental factors 12 ; however, the molecular mechanisms are still not well understood. Previously, we focused on a single-

Fat and lean pig breeds show obvious differences in meat quality characteristics including the fatty acid composition of muscle. However, the molecular mechanism underlying these phenotypes differences remains unknown. This study compared meat quality traits between Lantang (a Chinese indigenous breed) and Landrace (a typical lean breed). The Lantang pigs showed higher L* values and intramuscular fat content, lower pH45min, pH24h and shear force in longissimus dorsi (LD) muscle than Landrace (P < 0.05). Fatty acid analysis demonstrated the lower monounsaturated fatty acids (MUFA) and higher polyunsaturated fatty acids (PUFA) percentage in Lantang LD than that in Landrace LD (P < 0.05). To further identify candidate genes for fatty acid composition, the transcriptome of LD muscle from the two breeds were measured by microarrays. There were 586 transcripts differentially expressed, of which 267 transcripts were highly expressed in Lantang pigs. After the validation by real-time quantitative PCR, 13 genes were determined as candidate genes for fatty acid composition of muscle, including Stearoyl-CoA desaturase (SCD). Then, a SCD over-expression plasmid was transfected into C2C12 cells to reveal the effect of SCD on the fatty acid composition in vitro. The results showed that SCD over-expression significantly increased PUFA proportion, while reduced that of saturated fatty acids (SFA) in C2C12 cells (P < 0.05). In summary, this study compared the differences of fatty acid composition and transcriptome in two breeds differing in meat quality, and further identified the novel role of SCD in the regulation of PUFA deposition.