Determining contributions of exogenous glucose and fructose to de novo fatty acid and glycerol synthesis in liver and adipose tissue

Silva, João C. P.; Marques, Cátia; Martins, Fátima O.; Viegas, Iván; Tavares, Ludgero C.; Macedo, M. Paula; Jones, John G.

doi:10.1016/j.ymben.2019.08.018

Cited by 38 publications

(54 citation statements)

References 37 publications

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“…Livers were ground under liquid N 2 and extracted with methyl tert -butyl ether as previously described 8 . For analysis of liver glucose, the aqueous phase was neutralized, lyophilized and analyzed directly by 13 C NMR.…”

Section: Methodsmentioning

confidence: 99%

“…To date, many of these studies have focused on the effects of these sugars on hepatic and systemic dyslipidemia and glucose tolerance 1 – 4 . High sugar feeding has been shown to promote hepatic de novo lipogenesis 5 – 7 , with both fructose and glucose components contributing to fatty acid and glycerol synthesis 8 . Several studies have also reported decreased glucose tolerance in rodents fed diets high in sucrose 1 , 3 , 4 with alterations in hepatic glucose metabolism considered to have greater roles in this pathology compared to systemic glucose clearance, at least in the early stages.…”

Section: Introductionmentioning

confidence: 99%

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Determining the contribution of a high-fructose corn syrup formulation to hepatic glycogen synthesis during ad-libitum feeding in mice

Nunzio

Belew

Torres

et al. 2020

Sci Rep

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Excessive sugar intake including high-fructose corn syrup (HFCS) is implicated in the rise of obesity, insulin resistance and non-alcoholic fatty liver disease. Liver glycogen synthesis is influenced by both fructose and insulin signaling. Therefore, the effect of HFCS on hepatic glycogenesis was evaluated in mice feeding ad-libitum. Using deuterated water: the fraction of glycogen derived from triose-P sources, Krebs cycle substrates, and direct pathway + cycling, was measured in 9 normal-chow fed mice (NC) and 12 mice fed normal chow plus a 55% fructose/45% glucose mix in the drinking water at 30% w/v (HFCS-55). This was enriched with [U- 13 C]fructose or [U- 13 C]glucose to determine the contribution of each to glycogenesis. For NC, direct pathway + cycling, Krebs cycle, and triose-P sources accounted for 66 ± 0.7%, 23 ± 0.8% and 11 ± 0.4% of glycogen synthesis, respectively. HFCS-55 mice had similar direct pathway + cycling (64 ± 1%) but lower Krebs cycle (12 ± 1%, p < 0.001) and higher triose-P contributions (24 ± 1%, p < 0.001). HFCS-55-fructose contributed 17 ± 1% via triose-P and 2 ± 0% via Krebs cycle. HFCS-55-glucose contributed 16 ± 3% via direct pathway and 1 ± 0% via Krebs cycle. In conclusion, HFCS-55 supplementation resulted in similar hepatic glycogen deposition rates. Indirect pathway contributions shifted from Krebs cycle to Triose-P sources reflecting HFCS-55-fructose utilization, while HFCS-55-glucose was incorporated almost exclusively by the direct pathway.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Determining the contribution of a high-fructose corn syrup formulation to hepatic glycogen synthesis during ad-libitum feeding in mice

Nunzio

Belew

Torres

et al. 2020

Sci Rep

Self Cite

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“…O in this setting as a means of determining fractional rates of exchange or turnover is entirely dependent on a natural-abundance 13 C reporter nucleus, whereas 2 H can be observed either independently of 13 C enrichment 14,25 or via fully resolved isotope shifts and/or coupling interactions with adjacent 13 C nuclei. 26,27 Therefore, compared with 2 H 2 O, the scope for integrating NMR measurements of metabolite enrichment from H 2…”

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confidence: 99%

Metabolic incorporation of H₂¹⁸O into specific glucose‐6‐phosphate oxygens by red‐blood‐cell lysates as observed by ¹³C isotope‐shifted NMR signals

et al. 2020

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Water enriched with hydrogen isotopes (2 H, 3 H) has been used extensively as a metabolic tracer for carbohydrate biosynthesis in animals and humans. 1-4 While these tracers can be easily delivered and are rapidly and homogenously distributed throughout tissues, incorporation of 2 H or Abbreviations: 2 H2O, water enriched with deuterium; H2 18 O, water enriched with oxygen-18; MAG, monoacetone glucose; KIE, kinetic isotope effect.

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“…In contrast to ge‐HSQC, miscalibration of the 13 C transmit power does not per se lead to lower a 13 C‐enrichment, due to the B1 insensitivity of the pulses used in the proposed approach. The higher 13 C signal (compared with ge‐HSQC) together with minimal 12 C artifact with the use of the BIRD filter will enable to track even the smaller contribution of labeled glucose 12 to form 13 C lipids (compared with the contribution from 13 C‐labeled fatty acids) in the hepatic fat pool. Thus, our proposed approach can now be used as an efficient and promising tool for 13 C tracking applications in vivo.…”

Section: Discussionmentioning

confidence: 99%

Application of a BIlinear Rotation Decoupling (BIRD) filter in combination with J‐difference editing for indirect ¹³C measurements in the human liver

Veeraiah

Brouwers

Wildberger

et al. 2020

Magnetic Resonance in Med

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Purpose Recently, we introduced a quantum coherence based method (ge‐HSQC) for indirect 13C‐MRS in the liver to track 13C‐labeled lipids into the hepatic lipid pool in vivo. This approach is more robust in case of respiratory motion, however, inherently leads to a signal loss of 50% when compared with a conventional J‐difference editing technique (JDE). Here, we intend to improve the robustness of a regular JDE (STEAM‐ACED) with the use of a BIlinear Rotation Decoupling (BIRD) filter to achieve 100% higher signal gain when compared with ge‐HSQC. Methods To determine the efficiency of the BIRD filter 1H‐[13C] lipid spectra were acquired on 3T from a peanut oil phantom, with three different MR sequences: ge‐HSQC, STEAM‐ACED, and the BIRD filter together with STEAM‐ACED (BIRD‐STEAM‐ACED). Finally, our proposed method is tested in vivo in five healthy volunteers with varying liver fat content. In these subjects we quantified the 1H‐[13C]‐signal from the hepatic lipid pool and determined 13C enrichment, which is expected to be 1.1% according to the natural abundance of 13C. Results The application of the proposed BIRD filter reduces the subtraction artifact of 1H‐[12C] lipid signal efficiently in JDE experiments, which leads to a signal gain of 100% of 1H‐[13C]‐lipid signals when compared with the ge‐HSQC. Phase distortions in vivo were minimal with the use of BIRD compared with STEAM‐ACED, which enabled us to robustly quantify the 13C‐enrichment in all five subjects. Conclusion The BIRD‐STEAM‐ACED sequence is an efficient and promising tool for 13C‐tracking experiments in the human liver in vivo.

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Determining contributions of exogenous glucose and fructose to de novo fatty acid and glycerol synthesis in liver and adipose tissue

Cited by 38 publications

References 37 publications

Determining the contribution of a high-fructose corn syrup formulation to hepatic glycogen synthesis during ad-libitum feeding in mice

Determining the contribution of a high-fructose corn syrup formulation to hepatic glycogen synthesis during ad-libitum feeding in mice

Metabolic incorporation of H₂¹⁸O into specific glucose‐6‐phosphate oxygens by red‐blood‐cell lysates as observed by ¹³C isotope‐shifted NMR signals

Application of a BIlinear Rotation Decoupling (BIRD) filter in combination with J‐difference editing for indirect ¹³C measurements in the human liver

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Determining contributions of exogenous glucose and fructose to de novo fatty acid and glycerol synthesis in liver and adipose tissue

Cited by 38 publications

References 37 publications

Determining the contribution of a high-fructose corn syrup formulation to hepatic glycogen synthesis during ad-libitum feeding in mice

Determining the contribution of a high-fructose corn syrup formulation to hepatic glycogen synthesis during ad-libitum feeding in mice

Metabolic incorporation of H218O into specific glucose‐6‐phosphate oxygens by red‐blood‐cell lysates as observed by 13C isotope‐shifted NMR signals

Application of a BIlinear Rotation Decoupling (BIRD) filter in combination with J‐difference editing for indirect 13C measurements in the human liver

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Product

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Metabolic incorporation of H₂¹⁸O into specific glucose‐6‐phosphate oxygens by red‐blood‐cell lysates as observed by ¹³C isotope‐shifted NMR signals

Application of a BIlinear Rotation Decoupling (BIRD) filter in combination with J‐difference editing for indirect ¹³C measurements in the human liver