Plasma sterol evidence for decreased absorption and increased synthesis of cholesterol in insulin resistance and obesity

Paramsothy, Pathmaja; Knopp, Robert H.; Kahn, Steven E.; Retzlaff, Barbara M.; Fish, Brian; Ma, Lina; Ostlund, Richard E.

doi:10.3945/ajcn.110.006668

Cited by 41 publications

(30 citation statements)

References 41 publications

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“…In contrast to the increased levels of cholesterol precursors, plant sterols such as sitosterol, campesterol, and stigmasterol, which partially reflect dietary sterol absorption, are decreased in obese subjects consuming controlled diets [7,9]. In this study, plant sterols tended to be slightly lower in overweight or obese children, in particular the levels of sitosterol and campesterol in obese boys were significantly lower (P < 0.001; Table 2).…”

Section: [ ( F I G _ 2 ) T D $ F I G ]contrasting

confidence: 55%

“…Serum lathosterol levels increase progressively with BMI [9], while weight loss is shown to reduce lathosterol levels [22]. In addition, visceral obesity and dyslipidaemic patients with greater visceral fat have significantly higher lathosterol levels and cholesterol synthesis [23,24].…”

Section: [ ( F I G _ 2 ) T D $ F I G ]mentioning

confidence: 99%

“…In obese patients, serum concentrations of cholesterol precursors, such as lanosterol, lathosterol, and desmosterol, are increased while levels of plant sterols, such as sitosterol and campesterol, are decreased [7][8][9]. The hepatic esterification of cholesterol [10,11] and the activity of cholesterol 7a-hydroxylase, which regulates the catabolism of cholesterol, are also upregulated in obese subjects [11].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Serum sterol profiling reveals increased cholesterol biosynthesis in childhood obesity

Son

Kim

Moon

et al. 2015

The Journal of Steroid Biochemistry and Molecular Biology

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Section: [ ( F I G _ 2 ) T D $ F I G ]contrasting

confidence: 55%

Section: [ ( F I G _ 2 ) T D $ F I G ]mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Serum sterol profiling reveals increased cholesterol biosynthesis in childhood obesity

Son

Kim

Moon

et al. 2015

The Journal of Steroid Biochemistry and Molecular Biology

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“…Of particular interest were associations for glycerol and lathosterol because prior studies had been small and replication was needed (Puhakainen et al , 1992;Paramsothy et al , 2011). Glycerol is a three-carbon molecule that forms the backbone of all triglycerides and blood levels of glycerol reflect the rate of fatty acid breakdown (Puhakainen et al , 1992;Venables et al , 2008).…”

Section: Discussionmentioning

confidence: 99%

Human metabolic correlates of body mass index

et al. 2013

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Background A high body mass index (BMI) is a major risk factor for several chronic diseases, but the biology underlying these associations is not well-understood. Dyslipidemia, inflammation, and elevated levels of growth factors and sex steroid hormones explain some of the increased disease risk, but other metabolic factors not yet identified may also play a role. Design In order to discover novel metabolic biomarkers of BMI, we used non-targeted metabolomics to assay 317 metabolites in blood samples from 947 participants and examined the cross-sectional associations between metabolite levels and BMI. Participants were from three studies in the United States and China. Height, weight, and potential confounders were ascertained by questionnaire (US studies) or direct measurement (Chinese study). Metabolite levels were measured using liquid-phase chromatography and gas chromatography coupled with mass spectrometry. We evaluated study-specific associations using linear regression, adjusted for age, gender, and smoking, and we estimated combined associations using random effects meta-analysis. Results The meta-analysis revealed 37 metabolites significantly associated with BMI, including 19 lipids, 12 amino acids, and 6 others, at the Bonferroni significance threshold (p<0.00016). Eighteen of these associations had not been previously reported, including histidine, an amino acid neurotransmitter, and butyrylcarnitine, a lipid marker of whole-body fatty acid oxidation. Heterogeneity by study was minimal (all Pheterogeneity >0.05). In total, 110 metabolites were associated with BMI at the p<0.05 level. Conclusion These findings establish a baseline for the BMI metabolome, and suggest new targets for researchers attempting to clarify mechanistic links between high BMIs and disease risk.

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“…Excess exposure to insulin is commonly seen in overweight or obese subjects with insulin resistance and hyperinsulinemia. Increased levels of cholesterol synthesis and plasma cholesterol are also frequently seen in these same subjects (44). Numerous studies have shown an association of the increased cholesterol level with the development of various cardiovascular disorders, which are tightly connected to mitochondrion-derived oxidative stress (19,45).…”

Section: Discussionmentioning

confidence: 98%

Prolonged Exposure to Insulin Induces Mitochondrion-Derived Oxidative Stress through Increasing Mitochondrial Cholesterol Content in Hepatocytes

Mei

Yang

et al. 2012

Endocrinology

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We addressed the link between excessive exposure to insulin and mitochondrion-derived oxidative stress in this study and found that prolonged exposure to insulin increased mitochondrial cholesterol in cultured hepatocytes and in mice and stimulated production of reactive oxygen species (ROS) and decreased the reduced glutathione to glutathione disulfide ratio in cultured hepatocytes. Exposure of isolated hepatic mitochondria to cholesterol alone promoted ROS emission. The oxidative stress induced by the prolonged exposure to insulin was prevented by inhibition of cholesterol synthesis with simvastatin. We further found that prolonged exposure to insulin decreased mitochondrial membrane potential and the increased ROS production came from mitochondrial respiration complex I. Finally, we observed that prolonged exposure to insulin decreased mitochondrial membrane fluidity in a cholesterol synthesis-dependent manner. Together our results demonstrate that excess exposure to insulin causes mitochondrion-derived oxidative stress through cholesterol synthesis in hepatocytes.

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Plasma sterol evidence for decreased absorption and increased synthesis of cholesterol in insulin resistance and obesity

Cited by 41 publications

References 41 publications

Serum sterol profiling reveals increased cholesterol biosynthesis in childhood obesity

Serum sterol profiling reveals increased cholesterol biosynthesis in childhood obesity

Human metabolic correlates of body mass index

Prolonged Exposure to Insulin Induces Mitochondrion-Derived Oxidative Stress through Increasing Mitochondrial Cholesterol Content in Hepatocytes

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