In vivo measurement of fatty acids and cholesterol synthesis using D2O and mass isotopomer analysis

Lee, W. N. P.; Bassilian, Sara; Ajie, Henry O.; Schoeller, Dale A.; Edmond, John; Bergner, E. A.; Byerley, Lauri O.

doi:10.1152/ajpendo.1994.266.5.e699

Cited by 100 publications

(144 citation statements)

References 16 publications

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“…We also assessed DNL in control, high-fat fed, and IRASOtreated rats using a deuterated water method (23)(24)(25). DNL was compared in two separate experiments: first in fat-fed rats and regular chow-fed rats and second between IRASO-treated rats and control ASO-treated rats.…”

Section: Insulin Receptor 2′-o-methoxyethyl Chimeric Antisense Oligonmentioning

confidence: 99%

Insulin-independent regulation of hepatic triglyceride synthesis by fatty acids

Vatner¹,

Majumdar²,

Kumashiro³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

188

134

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A central paradox in type 2 diabetes is the apparent selective nature of hepatic insulin resistance-wherein insulin fails to suppress hepatic glucose production yet continues to stimulate lipogenesis, resulting in hyperglycemia, hyperlipidemia, and hepatic steatosis. Although efforts to explain this have focused on finding a branch point in insulin signaling where hepatic glucose and lipid metabolism diverge, we hypothesized that hepatic triglyceride synthesis could be driven by substrate, independent of changes in hepatic insulin signaling. We tested this hypothesis in rats by infusing [U-13 C] palmitate to measure rates of fatty acid esterification into hepatic triglyceride while varying plasma fatty acid and insulin concentrations independently. These experiments were performed in normal rats, high fat-fed insulin-resistant rats, and insulin receptor 2′-O-methoxyethyl chimeric antisense oligonucleotide-treated rats. Rates of fatty acid esterification into hepatic triglyceride were found to be dependent on plasma fatty acid infusion rates, independent of changes in plasma insulin concentrations and independent of hepatocellular insulin signaling. Taken together, these results obviate a paradox of selective insulin resistance, because the major source of hepatic lipid synthesis, esterification of preformed fatty acids, is primarily dependent on substrate delivery and largely independent of hepatic insulin action.nonalcoholic fatty liver disease | hepatic insulin resistance | lipogenesis | esterification | mass spectrometry

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Section: Insulin Receptor 2′-o-methoxyethyl Chimeric Antisense Oligonmentioning

confidence: 99%

Insulin-independent regulation of hepatic triglyceride synthesis by fatty acids

Vatner¹,

Majumdar²,

Kumashiro³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

188

134

View full text Add to dashboard Cite

show abstract

“…This fitting process (described in detail in Refs. 45 extension of palmitate to C18:0 stearate (versus salvage) by elongation was calculated based on the extra ϩ2 mass labeling in stearate, corresponding to the incorporation of an extra labeled acetyl unit, compared with the expected mass labeling based on the mass distribution in palmitate (46). Upon LPS stimulation for 24 h, incorporation of 13 C label from glucose to acetyl-CoA increased to 36% (Fig.…”

Section: Stimulation Of B Lymphocytes With Lps Leads Tomentioning

confidence: 99%

Glucose-dependent de Novo Lipogenesis in B Lymphocytes

Dufort

Gumina

et al. 2014

Journal of Biological Chemistry

145

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Background:The metabolic requirements underlying B lymphocyte differentiation are poorly understood. Results: Differentiation is accompanied by glucose metabolism into fatty acid and cholesterol synthesis, mediated by ATPcitrate lyase (ACLY). Conclusion: ACLY-dependent lipogenesis is required for several phenotypic changes defining plasma cell differentiation. Significance: This study proposes a critical role for ACLY coupled glucose-dependent de novo lipogenesis in LPS-induced B lymphocyte differentiation.

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“…Note that to compare the data, the labeling of water should be multiplied by ϳ7 because each carbon-bound hydrogen of glucose can be derived from water, i.e. at relatively low labeling of body water (precursor labeling), the total 2 H labeling of a product is approximately equal to the number of copies of the precursor (n) multiplied by the labeling of the precursor (18). Thus, the data reported by Chen et al (7) suggest that less than one of the seven carbon-bound hydrogens was labeled.…”

Section: Figurementioning

confidence: 99%

Triglyceride Synthesis in Epididymal Adipose Tissue

Bederman

Foy

Chandramouli

et al. 2009

Journal of Biological Chemistry

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The obesity epidemic has generated interest in determining the contribution of various pathways to triglyceride synthesis, including an elucidation of the origin of triglyceride fatty acids and triglyceride glycerol. We hypothesized that a dietary intervention would demonstrate the importance of using glucose versus non-glucose carbon sources to synthesize triglycerides in white adipose tissue. C57BL/6J mice were fed either a low fat, high carbohydrate (HC) diet or a high fat, carbohydrate-free (CF) diet and maintained on 2 H 2 O (to determine total triglyceride dynamics) or infused with [6,6-2 H]glucose (to quantify the contribution of glucose to triglyceride glycerol). The 2 H 2 O labeling data demonstrate that although de novo lipogenesis contributed ϳ80% versus ϳ5% to the pool of triglyceride palmitate in HC-versus CF-fed mice, the epididymal adipose tissue synthesized ϳ1.5-fold more triglyceride in CF-versus HC-fed mice, i.e. 37 ؎ 5 versus 25 ؎ 3 mol ؋ day ؊1 . The [6,6-2 H]glucose labeling data demonstrate that ϳ69 and ϳ28% of triglyceride glycerol is synthesized from glucose in HC-versus CF-fed mice, respectively. Although these data are consistent with the notion that non-glucose carbon sources (e.g. glyceroneogenesis) can make substantial contributions to the synthesis of triglyceride glycerol (i.e. the absolute synthesis of triglyceride glycerol from non-glucose substrates increased from ϳ8 to ϳ26 mol ؋ day ؊1 in HC-versus CF-fed mice), these observations suggest (i) the importance of nutritional status in affecting flux rates and (ii) the operation of a glycerol-glucose cycle.Epidemiological trends in the development of obesity (1-4) and its association with various diseases have generated interest in the study of lipid synthesis and mobilization. In particular, new methods have been developed for quantifying rates of triglyceride turnover in vivo (5-8). For example, using 2

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In vivo measurement of fatty acids and cholesterol synthesis using D2O and mass isotopomer analysis

Cited by 100 publications

References 16 publications

Insulin-independent regulation of hepatic triglyceride synthesis by fatty acids

Insulin-independent regulation of hepatic triglyceride synthesis by fatty acids

Glucose-dependent de Novo Lipogenesis in B Lymphocytes

Triglyceride Synthesis in Epididymal Adipose Tissue

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