Browsing by Author "Pahlavani, Mandana (TTU)"
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Item An integrative transcriptomic approach to identify depot differences in genes and microRNAs in adipose tissues from high fat fed mice(2018) Wijayatunga, Nadeeja N. (TTU); Pahlavani, Mandana (TTU); Kalupahana, Nishan S. (TTU); Kottapalli, Kameswara Rao (TTU); Gunaratne, Preethi H.; Coarfa, Cristian; Ramalingam, Latha (TTU); Moustaid-Moussa, Naima (TTU)Obesity contributes to metabolic disorders such as diabetes and cardiovascular disease. Characterization of differences between the main adipose tissue depots, white (WAT) [including subcutaneous (SAT) and visceral adipose tissue (VAT)] and brown adipose tissue (BAT) helps to identify their roles in obesity. Thus, we studied depot-specific differences in whole transcriptome and miRNA profiles of SAT, VAT and BAT from high fat diet (HFD/45% of calories from fat) fed mice using RNA sequencing and small RNA-Seq. Using quantitative real-time polymerase chain reaction, we validated depot-specific differences in endoplasmic reticulum (ER) stress related genes and miRNAs using mice fed a HFD vs. low fat diet (LFD/10% of calories from fat). According to the transcriptomic analysis, lipogenesis, adipogenesis, inflammation, endoplasmic reticulum (ER) stress and unfolded protein response (UPR) were higher in VAT compared to BAT, whereas energy expenditure, fatty acid oxidation and oxidative phosphorylation were higher in BAT than in VAT of the HFD fed mice. In contrast to BAT, ER stress marker genes were significantly upregulated in VAT of HFD fed mice than the LFD fed mice. For the first time, we report depot specific differences in ER stress related miRNAs including; downregulation of miR-125b-5p, upregulation miR-143-3p, and miR-222-3p in VAT following HFD and upregulation of miR-30c-2-3p only in BAT following a HFD in mice than the LFD mice. In conclusion, HFD differentially regulates miRNAs and genes in different adipose depots with significant induction of genes related to lipogenesis, adipogenesis, inflammation, ER stress, and UPR in WAT compared to BAT.Item Discordant dose-dependent metabolic effects of eicosapentanoic acid in diet-induced obese mice(2020) Pahlavani, Mandana (TTU); Ramalingam, Latha (TTU); Miller, Emily K. (TTU); Davis, Hanna (TTU); Scoggin, Shane (TTU); Moustaid-Moussa, Naima (TTU)Obesity is a widespread epidemic that increases the risk for several metabolic diseases. Despite several beneficial health effects of eicosapentaenoic acid (C20:5n-3, EPA), previous studies have used very high doses of EPA. In this study, dose-dependent effects of EPA on metabolic outcomes were determined in diet-induced obese mice. We used B6 male mice, fed high-fat diet (HF, 45% kcal fat) or HF diet supplemented with 9, 18, and 36 g/kg of EPA-enriched fish oil for 14 weeks. We conducted metabolic phenotyping during the feeding period, and harvested tissues and blood at termination. Only mice fed 36 g/kg of EPA significantly (p < 0.05) lowered body weight, fat content and epididymal fat pad weight, compared to HF. Both 18 and 36 g/kg doses of EPA significantly increased glucose clearance and insulin sensitivity, compared to HF or 9 g/kg of EPA. Locomotor activity was significantly increased with both 18 and 36 g/kg doses of EPA. Interestingly, all doses of EPA compared to HF, significantly increased energy expenditure and oxygen consumption and significantly reduced serum insulin, leptin, and triglycerides levels. These results demonstrate weight-and adiposity-independent metabolic benefits of EPA, at doses comparable to those currently used to treat hypertriglyceridemia.Item Eicosapentaenoic acid regulates inflammatory pathways through modulation of transcripts and mirna in adipose tissue of obese mice(2020) Ramalho, Theresa (TTU); Pahlavani, Mandana (TTU); Kalupahana, Nishan (TTU); Wijayatunga, Nadeeja (TTU); Ramalingam, Latha (TTU); Jancar, Sonia; Moustaid‐moussa, Naima (TTU)This study aims to investigate the global profiling of genes and miRNAs expression to explore the regulatory effects of eicosapentaenoic acid (EPA) in visceral adipose tissue (VAT) of obese mice. We used male mice, fed either a high‐fat diet (HF) or HF supplemented with EPA (HF‐ EPA), for 11 weeks. RNA, and small RNA profiling, were performed by RNAseq analysis. We conducted analyses using Ingenuity Pathway Analysis software (IPA®) and validated candidate genes and miRNAs related to lipid mediators and inflammatory pathways using qRT‐PCR. We identified 153 genes differentially downregulated, and 62 microRNAs differentially expressed in VAT from HF‐EPA compared to HF. Genes with a positive association with inflammation, chemotaxis, insulin resistance, and inflammatory cell death, such as Irf5, Alox5ap, Tlrs, Cd84, Ccr5, Ccl9, and Casp1, were downregulated by EPA. Moreover, EPA significantly reduced LTB4 levels, a lipid mediator with a central role in inflammation and insulin resistance in obesity. The pathways and mRNA/microRNA interactions identified in our study corroborated with data validated for inflammatory genes and miRNAs. Together, our results identified key VAT inflammatory targets and pathways, which are regulated by EPA. These targets merit further investigation to better understand the protective mechanisms of EPA in obesity‐associated inflammation.Item Sex-Dependent Effects of Eicosapentaenoic Acid on Hepatic Steatosis in UCP1 Knockout Mice(2021) Albracht-Schulte, Kembra (TTU); Wilson, Savanna (TTU); Johnson, Paige (TTU); Pahlavani, Mandana (TTU); Ramalingam, Latha (TTU); Goonapienuwala, Bimba (TTU); Kalupahana, Nishan S. (TTU); Festuccia, William T.; Scoggin, Shane (TTU); Kahathuduwa, Chanaka N. (TTUHSC); Moustaid-Moussa, Naima (TTU)Visceral obesity may be a driving factor in nonalcoholic fatty liver disease (NAFLD) development. Previous studies have shown that the omega-3 polyunsaturated fatty acid, eicosapentaenoic acid (EPA), ameliorates obesity in high-fat (HF) fed male, C57Bl/6 mice at thermoneutral conditions, independent of uncoupling protein 1 (UCP1). Our goals herein were to investigate sex-dependent mechanisms of EPA in the livers of wild type (WT) and UCP1 knockout (KO) male and female mice fed a HF diet (45% kcal fat; WT-HF, KO-HF) with or without supplementation of 36 g/kg EPA (WT-EPA, KO-EPA). KO significantly increased body weight in males, with no significant reductions with EPA in the WT or KO groups. In females, there were no significant differences in body weight among KO groups and no effects of EPA. In males, liver TGs were significantly higher in the KO-HF group and reduced with EPA, which was not observed in females. Accordingly, gene and protein markers of mitochondrial oxidation, peroxisomal biogenesis and oxidation, as well as metabolic futile cycles were sex-dependently impacted by KO and EPA supplementation. These findings suggest a genotypic difference in response to dietary EPA supplementation on the livers of male and female mice with diet-induced obesity and housed at thermoneutrality.