Genetic control of<i>de novo</i>lipogenesis: role in diet-induced obesity

Strable, Maggie S.; Ntambi, James M.

doi:10.3109/10409231003667500

Cited by 369 publications

(313 citation statements)

References 119 publications

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“…Moreover, Chrebp was impaired in the PHanov group, showing a correlation with basal glucose levels in those animals. These data are in accordance with that described by other authors showing that in the hyperinsulinemic and even more in the IR states, SREBP1-c transcription is stimulated and could lead to de novo fatty acid synthesis (Browning & Horton 2004, Strable & Ntambi 2010. The third transcription factor studied, also involved in the regulation of lipogenesis, was PPARγ.…”

Section: Discussionsupporting

confidence: 92%

“…To assess the lipogenic pathway, we evaluated the role of three transcription factors involved in the regulation of de novo lipogenesis. Two of them, SREBP and CHREBP, are regulated by insulin and glucose levels, respectively, and both regulate the expression of genes encoding lipogenic enzymes (Browning & Horton 2004, Strable & Ntambi 2010. Our results showed that the PH groups presented high levels of Srebp, consistent with the high levels of serum insulin found in PH animals.…”

Section: Discussionsupporting

confidence: 82%

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Prenatal hyperandrogenism induces alterations that affect liver lipid metabolism

Abruzzese

Heber

Ferreira

et al. 2016

Journal of Endocrinology

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Prenatal hyperandrogenism is hypothesized as one of the main factors contributing to the development of polycystic ovary syndrome (PCOS). PCOS patients have high risk of developing fatty liver and steatosis. This study aimed to evaluate the role of prenatal hyperandrogenism in liver lipid metabolism and fatty liver development. Pregnant rats were hyperandrogenized with testosterone. At pubertal age, the prenatally hyperandrogenized (PH) female offspring displayed both ovulatory (PHov) and anovulatory (PHanov) phenotypes that mimic human PCOS features. We evaluated hepatic transferases, liver lipid content, the balance between lipogenesis and fatty acid oxidation pathway, oxidant/antioxidant balance and proinflammatory status. We also evaluated the general metabolic status through growth rate curve, basal glucose and insulin levels, glucose tolerance test, HOMA-IR index and serum lipid profile. Although neither PH group showed signs of liver lipid content, the lipogenesis and fatty oxidation pathways were altered. The PH groups also showed impaired oxidant/antioxidant balance, a decrease in the proinflammatory pathway (measured by prostaglandin E2 and cyclooxygenase-2 levels), decreased glucose tolerance, imbalance of circulating lipids and increased risk of metabolic syndrome. We conclude that prenatal hyperandrogenism generates both PHov and PHanov phenotypes with signs of liver alterations, imbalance in lipid metabolism and increased risk of developing metabolic syndrome. The anovulatory phenotype showed more alterations in liver lipogenesis and a more impaired balance of insulin and glucose metabolism, being more susceptible to the development of steatosis. Androgen excess alters liver lipid metabolism

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 82%

Prenatal hyperandrogenism induces alterations that affect liver lipid metabolism

Abruzzese

Heber

Ferreira

et al. 2016

Journal of Endocrinology

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“…The transcription factor ChREBP has emerged as a major mediator of glucose action in the regulation of both glycolysis and lipogenesis. It acts in synergy with SREBP to induce the expression of lipogenic genes such as ACC and FAS as the direct targets of ChREBP (Denechaud et al, 2008;Strable and Ntambi, 2010). Liverspecific inhibition of ChREBP markedly improved hepatic steatosis by specifically decreasing lipogenesis in obese ob/ ob mice (Dentin et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Effects of inhibiting PI3K-Akt-mTOR pathway on lipid metabolism homeostasis in goose primary hepatocytes

Liu

Han

Wan

et al. 2016

Animal

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Phosphatidylinositol-3 kinases (PI3K)-Protein kinase B (Akt)-mammalian target of rapamycin (mTOR) pathway plays an important role in the synthesis and secretion of triacylglycerol. However, the mechanism of PI3K-Akt-mTOR pathway in regulating lipid metabolism of goose liver was poorly understood. The purpose of this study was to determine how PI3K-Akt-mTOR pathway regulating lipid metabolic homeostasis in goose hepatocytes. Goose primary hepatocytes were treated with different PI3K-Akt-mTOR signal inhibitors (LY294002, rapamycin and NVP-BEZ235) for 24 h. The results showed that these inhibitors evidently inhibited PI3K-Akt-mTOR downstream signaling. Meanwhile, these PI3K-Akt-mTOR inhibitors reduced intracellular lipid accumulation, decreased the mRNA expression and protein content of genes involved in the de novo fatty acid synthesis, while increased the transcriptional and protein level of key factors involved in fatty acid oxidation and very low density lipoprotein (VLDL) assembly and secretion. Conclusion: These findings suggested that the reduction of lipids accumulation induced-by inhibiting PI3K-Akt-mTOR pathway was closely linked to the decrease of lipogenesis, the increase of fatty acids oxidation, and the increase of VLDL assembly and secretion in goose hepatocytes.

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“…The expression levels of selected genes involved in lipid uptake, transport, lipolysis, de novo lipogenesis and fatty acid oxidation were analysed (Table 2). Additionally, we analysed the expression of the transcription factors PPARd and LXRa which have been described as fatty acid sensors regulating genes involved in lipid metabolism (Sanderson et al 2009;Strable and Ntambi 2010). Whereas there were no differences in PBMC gene expression levels of UCP2, HSL and PPARd between normal weight and MHO subjects, ARO subjects had significantly lower expression levels of these genes compared with both normal weight subjects (P = 0.041, P = 0.035 and P = 0.05, respectively) and MHO subjects (P = 0.003, P = 0.003 and P = 0.006, respectively) (Fig.…”

Section: Pbmc Gene Expressionmentioning

confidence: 99%

Altered expression of genes involved in lipid metabolism in obese subjects with unfavourable phenotype

et al. 2013

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Obesity (BMI C30 kg/m 2 ) increases the risk of developing lifestyle-related diseases. A subgroup of obese individuals has been described as ''metabolically healthy, but obese'' (MHO). In contrast to at-risk obese (ARO), the MHO phenotype is defined by a favourable lipid profile and a normal or only slightly affected insulin sensitivity, despite the same amount of body fat. The objective was to characterize the metabolic phenotype of MHO subjects. We screened a variety of genes involved in lipid metabolism and inflammation in peripheral blood mononuclear cells (PBMC). Obese subjects (men and women; 18-70 years) with BMI C30 kg/m 2 were characterized as MHO (n = 9) or as ARO (n = 10). In addition, eleven healthy, normal weight subjects characterized as healthy by the same criteria as described for the MHO subjects were included. We found that with similar weight, total fat mass and fat mass distribution, the ARO subjects have increased plasma levels of gamma-glutamyl transpeptidase and free fatty acids. This group also has altered expression levels of a number of genes linked to lipid metabolism in PBMC with reduced gene expression levels of uncoupling protein 2, hormone-sensitive lipase and peroxisome proliferatoractivated receptor d compared with MHO subjects. The present metabolic differences between subgroups of obese subjects may contribute to explain some of the underlying mechanisms causing the increased risk of disease among ARO subjects compared with MHO subjects.

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Genetic control ofde novolipogenesis: role in diet-induced obesity

Cited by 369 publications

References 119 publications

Prenatal hyperandrogenism induces alterations that affect liver lipid metabolism

Prenatal hyperandrogenism induces alterations that affect liver lipid metabolism

Effects of inhibiting PI3K-Akt-mTOR pathway on lipid metabolism homeostasis in goose primary hepatocytes

Altered expression of genes involved in lipid metabolism in obese subjects with unfavourable phenotype

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