Alterations in hepatic one-carbon metabolism and related pathways following a high-fat dietary intervention

Rubio‐Aliaga, Isabel; Roos, Baukje de; Sailer, Manuela; McLoughlin, Gráinne; Boekschoten, Mark V.; Erk, Marjan van; Bachmair, Eva-Maria; Schothorst, Evert M. van; Keijer, Jaap; Coort, Susan L.; Evelo, Chris T.; Gibney, Michael J.; Daniel, Hannelore; Müller, Michael; Kleemann, Robert; Brennan, Lorraine

doi:10.1152/physiolgenomics.00179.2010

Cited by 66 publications

(60 citation statements)

References 48 publications

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“…Notably, in these 2 studies, weight gain did not increase beyond that of the control. On the other hand, 2 similar studies of longer duration reported MAT1a upregulation (41,42) concomitant with increased fat gain. Zucker fatty rats, in which a leptin receptor mutation produces hyperphagia and obesity, have increased hepatic SAM (43).…”

Section: Discussionmentioning

confidence: 85%

S-Adenosylmethionine Is Associated with Fat Mass and Truncal Adiposity in Older Adults

Elshorbagy

Nijpels

Valdivia-Garcia

et al. 2013

The Journal of Nutrition

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S-adenosylmethionine (SAM) is synthesized from methionine, which is abundant in animal-derived protein, in an energy-consuming reaction. SAM and S-adenosylhomocysteine (SAH) correlate with body mass index (BMI). Plasma total concentration of the SAM-associated product cysteine (tCys) correlates with fat mass in humans and cysteine promotes adiposity in animals. In a cross-sectional study of 610 participants, we investigated whether SAM and SAH are associated with BMI via lean mass or fat mass and dietary protein sources as determinants of SAM and tCys concentrations. Plasma SAM was not associated with lean mass, but mean adjusted fat mass increased from 24 kg (95% CI: 22.6, 25.1) to 30 kg (95% CI: 28.7, 31.3) across SAM quartiles (P < 0.001) and trunk fat:total fat ratio increased from 0.48 to 0.52 (P < 0.001). Erythrocyte SAM was also positively associated with fat mass and trunk fat:total fat ratio. The association of SAM with fat mass was not weakened by adjustment for serum tCys, lipids, creatinine, or dietary or lifestyle confounders. Concentrations of the SAM precursor, methionine, and the SAM product, SAH, were not independently associated with adiposity. Intake of animal-derived protein was not related to serum methionine but was positively associated with plasma SAM (partial r = 0.11) and serum tCys (partial r = 0.13; P < 0.05 for both after adjustment for age, gender, and total energy intake). In conclusion, plasma SAM, but not methionine, is independently associated with fat mass and truncal adiposity, suggesting increased conversion of methionine to SAM in obese individuals. Prospective studies are needed to investigate the interactions among dietary energy and animal protein content, SAM concentrations, and change in body weight and cardiometabolic risk.

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Section: Discussionmentioning

confidence: 85%

S-Adenosylmethionine Is Associated with Fat Mass and Truncal Adiposity in Older Adults

Elshorbagy

Nijpels

Valdivia-Garcia

et al. 2013

The Journal of Nutrition

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“…Metabolomics is powerful in that it provides unbiased datasets which can be analysed to infer mechanistic information [25,26]. For example, metabolomic studies of liver from mice or rats subjected to an HFD have demonstrated significant diet induced changes in lysolipids, choline, fatty acids and associated intermediates and amino acids [27–29]. The global summary of the present analysis indicated that 48 of 341 metabolites were significantly elevated in liver of AdKO mice after 6 weeks of HFD, whereas 99 were reduced.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic profiling in liver of adiponectin-knockout mice uncovers lysophospholipid metabolism as an important target of adiponectin action

Liu

Sen

Wannaiampikul

et al. 2015

Biochemical Journal

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Adiponectin mediates anti-diabetic effects via increasing hepatic insulin sensitivity and direct metabolic effects. In the present study, we conducted a comprehensive and unbiased metabolomic profiling of liver tissue from AdKO (adiponectin-knockout) mice, with and without adiponectin supplementation, fed on an HFD (high-fat diet) to derive insight into the mechanisms and consequences of insulin resistance. Hepatic lipid accumulation and insulin resistance induced by the HFD were reduced by adiponectin. The HFD significantly altered levels of 147 metabolites, and bioinformatic analysis indicated that one of the most striking changes was the profile of increased lysophospholipids. These changes were largely corrected by adiponectin, at least in part via direct regulation of PLA2 (phospholipase A2) as palmitate-induced PLA2 activation was attenuated by adiponectin in primary hepatocytes. Notable decreases in several glycerolipids after the HFD were reversed by adiponectin, which also corrected elevations in several diacyglycerol and ceramide species. Our data also indicate that stimulation of ω-oxidation of fatty acids by the HFD is enhanced by adiponectin. In conclusion, this metabolomic profiling approach in AdKO mice identified important targets of adiponectin action, including PLA2, to regulate lysophospholipid metabolism and ω-oxidation of fatty acids.

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“…Samples were treated according to the manufacturer's instructions and analyzed via LC-MS/MS (3200QTRAP LC/MS/MS, Applied Biosystems). Spectra were processed using the Analyst ® 1.5 Software [27]. HPLC-MS/MS detection of hepatic SAM and SAH levels was performed using a Waters 2795 alliance HT, coupled to a Quattro Micro API tandem mass spectrometer (Waters Corporation) according to the previously described methodology with minor modifications [28].…”

Section: Methodsmentioning

confidence: 99%

Methyl-donor supplementation in obese mice prevents the progression of NAFLD, activates AMPK and decreases acyl-carnitine levels

Dahlhoff

Worsch

Sailer

et al. 2014

Molecular Metabolism

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Non-alcoholic fatty liver disease (NAFLD) results from increased hepatic lipid accumulation and steatosis, and is closely linked to liver one-carbon (C1) metabolism. We assessed in C57BL6/N mice whether NAFLD induced by a high-fat (HF) diet over 8 weeks can be reversed by additional 4 weeks of a dietary methyl-donor supplementation (MDS). MDS in the obese mice failed to reverse NAFLD, but prevented the progression of hepatic steatosis associated with major changes in key hepatic C1-metabolites, e.g. S-adenosyl-methionine and S-adenosyl-homocysteine. Increased phosphorylation of AMPK-α together with enhanced β-HAD activity suggested an increased flux through fatty acid oxidation pathways. This was supported by concomitantly decreased hepatic free fatty acid and acyl-carnitines levels. Although HF diet changed the hepatic phospholipid pattern, MDS did not. Our findings suggest that dietary methyl-donors activate AMPK, a key enzyme in fatty acid β-oxidation control, that mediates increased fatty acid utilization and thereby prevents further hepatic lipid accumulation.

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Alterations in hepatic one-carbon metabolism and related pathways following a high-fat dietary intervention

Cited by 66 publications

References 48 publications

S-Adenosylmethionine Is Associated with Fat Mass and Truncal Adiposity in Older Adults

S-Adenosylmethionine Is Associated with Fat Mass and Truncal Adiposity in Older Adults

Metabolomic profiling in liver of adiponectin-knockout mice uncovers lysophospholipid metabolism as an important target of adiponectin action

Methyl-donor supplementation in obese mice prevents the progression of NAFLD, activates AMPK and decreases acyl-carnitine levels

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