Fatty acid synthesis in liver and adipose tissue

Pearce, J.

doi:10.1079/pns19830031

Cited by 49 publications

(36 citation statements)

References 97 publications

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“…However, several lines of evidence have proved that the WAT played a more important role in de novo lipogenesis than the liver (Pearce 1983;Swierczynski et al 2000). Parasympathetic inputs to adipose tissue modulates glucose uptake and free fatty acid metabolis (Kreier et al 2002) and has selective effects on local hormone synthesis controlling the specific activities of lipogenic enzymes (Fliers et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Acute effects of oral olanzapine treatment on the expression of fatty acid and cholesterol metabolism-related gene in rats

et al. 2015

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. (2015). Acute effects of oral olanzapine treatment on the expression of fatty acid and cholesterol metabolism-related gene in rats. Life Sciences, Acute effects of oral olanzapine treatment on the expression of fatty acid and cholesterol metabolism-related gene in rats AbstractAims Second-generation antipsychotic drugs (SGAs) have a high risk for serious metabolic side-effects including dyslipidemia. This study aimed to investigate the acute effects of oral olanzapine treatment on the expression of genes for fatty acid and cholesterol biosynthesis in rats. Main methods Female Sprague-Dawley rats were treated orally with olanzapine (1 mg/kg, equivalent to a human clinical dose of 10 mg) via selfadministration aimed to measure pharmacokinetics. Based on the pharmacokinetic analysis, the acute effects of olanzapine on sterol regulatory element binding protein (SREBP)-related fatty acid/cholesterol metabolism genes were investigated in the liver and perirenal white adipose tissue (WAT) by Real-time quantitative PCR. Key findings A pharmacokinetic analysis demonstrated that the maximum concentration of olanzapine in plasma (Cmax) occurred at 6 h with a peak concentration of 276.5 ng/ml after a single oral treatment and with a plasma elimination half-life of 3.5 h after peak. The mRNA expression of SREBP-2 and target genes for cholesterol synthesis and transport was increased 1.9 8.8 fold compared with the control at 6 h after olanzapine administration but returned to basal level at 12 h post-treatment, while the increased mRNA expression of SREBP-1c and its targeted fatty acid-related genes appeared at both 6 h and 12 h post-treatment. Significance The present study provided evidence that olanzapine at a clinically-relevant dose caused abnormal expression of genes involved in lipid metabolism in the liver and WAT. These results suggest that olanzapine may cause dyslipidemia side-effects through direct effects on lipid biosynthesis and efflux genes associated with SREBP-stimulated transcriptional changes. Disciplines Medicine and Health Sciences Publication DetailsLiu, X., Deng, C., Cao, S., Gong, J., Wang, B. & Hu, C. (2015). Acute effects of oral olanzapine treatment on the expression of fatty acid and cholesterol metabolism-related gene in rats. Life Sciences, 128 72-78. Second-generation antipsychotic drugs (SGAs) have a high risk for serious metabolic sideeffects including dyslipidemia. This study aimed to investigate the acute effects of oral olanzapine treatment on the expression of genes for fatty acid and cholesterol biosynthesis in rats. Main methods:Female Sprague-Dawley rats were treated orally with olanzapine (1 mg/kg, equivalent to human clinical dose of 10 mg) via self-administration aimed to measure pharmacokinetics.Based on the pharmacokinetic analysis, the acute effects of olanzapine on SREBP-related fatty acid/cholesterol metabolism genes were investigated in the liver and perirenal white adipose tissue (WAT) by Real-time quantitative PCR. Key findings:A pharmacokinetic analysis demonstrated that ...

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Section: Discussionmentioning

confidence: 99%

Acute effects of oral olanzapine treatment on the expression of fatty acid and cholesterol metabolism-related gene in rats

et al. 2015

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“…In humans, de novo lipogenesis occurs predominantly in the liver; however, both AT and the liver are significantly involved in murine de novo lipogenesis [10,23,138]. Furthermore, Scd1 is highly expressed in murine AT [10,23,138], and SCD1 expression in human AT is considerably high compared to any other tissue [139].…”

Section: General Overview Of Scd1 In Adipose Tissue Modelsmentioning

confidence: 92%

Elucidating the roles of stearoyl-CoA desaturase 1 in adipocyte fatty acid metabolism and cellular function

Ralston

2015

Appl. Physiol. Nutr. Metab.

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Worldwide obesity rates have risen to epidemic proportions, with over 600 million obese individuals across the globe. These individuals are prone to obesity-related health complications including type 2 diabetes, hypertension, cancer and cardiovascular disease. Obesity also coincides with the expansion of adipose tissue (AT), which has an important role storing excess calories in the form of triacylglycerol (TAG) within adipocyte lipid droplets. The predominant fatty acids (FAs) comprising adipocyte TAGs are monounsaturated FAs (MUFAs), which are produced by stearoyl-CoA desaturase 1 (SCD1). Specifically, SCD1 converts saturated FAs palmitate (PA) and stearate (SA) into palmitoleate (PMA) and oleate (OA), respectively.Interestingly, whole-body SCD1-deficiency is associated with reduced lipogenesis and adiposity.This places SCD1 as a potential target for obesity therapies; however, our understanding of the mechanisms linking SCD1 with changes in adipocyte function remains unclear. This thesis provides important new insights into how SCD1 impacts adipocyte FA metabolism and cellular function. Using a specific SCD1 inhibitor, changes in lipid metabolism, global gene expression, inflammation, cellular stress and basal insulin signaling were assessed in 3T3-L1 adipocytes.Results demonstrated that SCD1 inhibition caused a reduction in TAGs and phospholipids, which coincided with the down-regulation of genes associated with the biosynthesis of these lipid fractions. Cellular diacylglyerols were increased with SCD1 inhibition and insulin signaling was partially impaired. In contrast, markers of cellular stress were unaltered. Furthermore, the FA composition of each lipid fraction was dramatically modified, with SCD1-inhibited adipocytes specifically up-regulating the elongation of PA to SA. Stable isotope tracer experiments revealed that this elongation was occurring via elongase 6. Additionally, reduced SCD1 activity in adipocytes exacerbated the effects of exogenous SA on markers or inflammation. Taken together, SCD1 activity has many indirect influences on adipocyte metabolism in addition to its role in FA desaturation. Importantly, SCD1 facilitates the storage of FAs in TAGs and the ability of adipocytes to handle exogenous FAs. SCD1 also prevents saturated FA and DAG accumulation, and preserves insulin signaling in adipocytes. Ultimately this thesis highlights the importance of SCD1 in the maintenance of adipocyte cellular function, and emphasizes the wide-ranging impact of SCD1 on adipocyte FA metabolism.iv

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“…Lipogenesis has been shown to be affected by many variables, including age and(or) body weight, sex, strain or breed, diet, feeding frequency, and hormones (Steele and Frobish, 1976;Hood, 1983;Pearce, 1983). In pigs, lipo genesis is low in young, nursing piglets and increases rapidly after the animals are weaned to a solid diet .…”

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confidence: 99%

“…The relative contributions of the liver and adipose tissue, as well as other tissues including skin, intestine, and muscle, to lipogenesis in rats and mice have varied in different experiments (Pearce, 1983), probably because of differences in diet, feeding pattern, and radioactive tracer used. The same contradictions have been seen in studies examining lipogenesis in humans.…”

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confidence: 99%

Metabolism of cholesterol and triglycerides in young pigs fed beef-based, soy-based, or conventional diets

Schade¹

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Fatty acid synthesis in liver and adipose tissue

Cited by 49 publications

References 97 publications

Acute effects of oral olanzapine treatment on the expression of fatty acid and cholesterol metabolism-related gene in rats

Acute effects of oral olanzapine treatment on the expression of fatty acid and cholesterol metabolism-related gene in rats

Elucidating the roles of stearoyl-CoA desaturase 1 in adipocyte fatty acid metabolism and cellular function

Metabolism of cholesterol and triglycerides in young pigs fed beef-based, soy-based, or conventional diets

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