Browsing by Subject "Triglycerides"
Now showing 1 - 5 of 5
- Results Per Page
- Sort Options
Item The Chylomicronemia Syndrome: an uncommon but potentially lethal form of hypertriglyceridemia(1991-07-25) Bilheimer, David W.Item Disorders of plasma triglyceride metabolism(1981-01-22) Bilheimer, David W.Item Ethnic Differences in Fatty Acid Oxidation(2014-02-04) Benjamin, Brian; Wada, Yasuyo; Vega, Gloria; Szuszkiewicz-Garcia, Magdalene; Grundy, ScottINTRODUCTION: Triglyceride levels of African Americans are significantly lower than those of Caucasians. This discrepancy complicates the recognition and diagnosis of metabolic disease in African Americans and represents a paradox in the metabolic health of African Americans. Many reasons for this difference have been explored including increased lipoprotein lipase activity, decreased hepatic lipase activity, and increased suppression of adipocyte lipolysis. Another possible explanation for this triglyceride discrepancy that has been sparsely explored is a difference in fatty acid oxidation between the two groups. The hypothesis of the present study is that the discrepancy in triglycerides can be explained, at least in part, by more efficient beta oxidation of fatty acids in the African American population. METHODS: A pilot study was initiated to examine whether a difference in beta oxidation of fatty acids between the two groups exists by examining the ratio of downstream metabolites of beta oxidation (beta hydroxybutyrate; BHB) to upstream metabolites (nonesterified fatty acids; NEFA). Healthy lean African American and Caucasian males were given a fat bolus (200 mg/kg Schepp's dairy heavy cream) hourly over a ten hour time period (fat tolerance test). BHB, NEFA, and plasma triglycerides were measured throughout the test. The data were plotted against time and area under the curve (AUC) was calculated for each plot using the trapezoid rule. The ratio of BHB to NEFA total AUC was calculated and compared between groups. One volunteer from the Caucasian group was excluded from analysis as an outlier based on fasting BHB levels (Grubb's test p<0.01). Groups were compared using 2 sample t-tests. RESULTS: Preliminary results (n=9 African Americans, n=8 Caucasians) demonstrate a trend, as predicted, for the ratio of BHB AUC to NEFA AUC to be higher in African Americans compared to Caucasians (p<0.05). Additionally, the BHB AUC is significantly higher in African Americans (p<0.05), further supporting the study hypothesis. CONCLUSIONS: Initial results suggest that healthy lean African American men may be more efficient oxidizers of fatty acids when compared to healthy lean Caucasian men. This difference could be a contributing factor to the triglyceride difference observed in African Americans and Caucasians. The study is still ongoing and further recruitment and analysis remains to be done.Item Fat: absorption and malabsorption(1992-04-09) Dietschy, John M.Item Identification of Cellular Sensors for Unsaturated Fatty Acids(2013-03-04) Kim, Hyeonwoo; DeBose-Boyd, Russell A.; Scherer, Philipp; Goodman, Joel M.In mammalian cells fatty acids (FAs) are required for the synthesis of membrane phospholipid components and energy generation. However, overaccumulation of FA is toxic. Accumulation of FAs prevents their further synthesis by stabilization of Insulin-induced gene 1(Insig-1), an ER membrane protein that inhibits proteolytic activation of sterol regulatory element binding protein-1 (SREBP-1), a transcription factor that activates all genes required for FA synthesis. This regulatory reaction is stimulated by unsaturated but not saturated FAs. Unsaturated FAs stabilize Insig-1 through disrupting the interaction between Insig-1 and UBX domain-containing protein 8 (Ubxd8), which recruits p97, a protein required for degradation of endoplasmic-reticulum (ER) membrane proteins, to Insig-1. Here, we identified Ubxd8, a protein that does not contain any previously recognized domains that bind FAs, as a sensor for unsaturated FAs. In cultured cells, we demonstrated that unsaturated FAs but not saturated FAs stimulated polymerization of Ubxd8 through bimolecular fluorescence complementation (BiFC) assays. In vitro, unsaturated but not saturated FAs also stimulated polymerization of purified recombinant Ubxd8. The effect of different FAs and their derivatives on polymerization of Ubxd8 in vitro correlated with their effect on stabilization of Insig-1 in cultured cells. Ubxd8 contains 3 domains, namely ubiquitin X (UBX), ubiquitin associated (UBA) and ubiquitin associating (UAS) domain. Deletion analysis showed that UAS domain was necessary and sufficient for polymerization of the protein in response to unsaturated FAs. Point mutations in UAS domain that disrupted its interaction with unsaturated FAs in vitro also impaired the ability of full length Ubxd8 to stabilize Insig-1 in response to unsaturated FAs in cultured cells. In addition to Ubxd8, the only other protein expressed in mammalian cells that contains a UAS domain similar to that of Ubxd8 is Fas-associated factor 1 (FAF1). We showed that unsaturated FAs also specifically induced polymerization of FAF1, and this polymerization was mediated by the UAS domain. The identification of UAS domain as a motif polymerizing upon interaction with unsaturated FAs should provide more insights into cellular responses to FAs.