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. 2009 Dec 23:8:64.
doi: 10.1186/1475-2840-8-64.

Lipogenesis in arterial wall and vascular smooth muscular cells: regulation and abnormalities in insulin-resistance

Nadjiba Hamlat  1 , Fabien Forcheron, Samia Negazzi, Peggy del Carmine, Patrick Feugier, Giampiero Bricca, Souhila Aouichat-Bouguerra, Michel Beylot
Affiliations

Lipogenesis in arterial wall and vascular smooth muscular cells: regulation and abnormalities in insulin-resistance

Nadjiba Hamlat et al. Cardiovasc Diabetol. .

Abstract

Background: Vascular smooth muscular cells (VSMC) express lipogenic genes. Therefore in situ lipogenesis could provide fatty acids for triglycerides synthesis and cholesterol esterification and contribute to lipid accumulation in arterial wall with aging and during atheroma.

Methods: We investigated expression of lipogenic genes in human and rat arterial walls, its regulation in cultured VSMC and determined if it is modified during insulin-resistance and diabetes, situations with increased risk for atheroma.

Results: Zucker obese (ZO) and diabetic (ZDF) rats accumulated more triglycerides in their aortas than their respective control rats, and this triglycerides content increased with age in ZDF and control rats. However the expression in aortas of lipogenic genes, or of genes involved in fatty acids uptake, was not higher in ZDF and ZO rats and did not increase with age. Expression of lipogenesis-related genes was not increased in human arterial wall (carotid endarterectomy) of diabetic compared to non-diabetic patients. In vitro, glucose and adipogenic medium (ADM) stimulated moderately the expression and activity of lipogenesis in VSMC from control rats. LXR agonists, but not PXR agonist, stimulated also lipogenesis in VSMC but not in arterial wall in vivo. Lipogenic genes expression was lower in VSMC from ZO rats and not stimulated by glucose or ADM.

Conclusion: Lipogenic genes are expressed in arterial wall and VSMC; this expression is stimulated (VSMC) by glucose, ADM and LXR agonists. During insulin-resistance and diabetes, this expression is not increased and resists to the actions of glucose and ADM. It is unlikely that this metabolic pathway contribute to lipid accumulation of arterial wall during insulin-resistance and diabetes and thus to the increased risk of atheroma observed in these situations.

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Figures

Figure 1
Figure 1
mRNA concentrations for genes involved in fatty acid synthesis (FAS, ACC1, Srebp-1c, ChREBP) and in uptake of fatty acids from plasma lipids (FAT, LPL, VLDLr) in aortas of control (CZ) and ZDF rats studied at the age of 7, 14 and 21 weeks. * p < 0.05, ** p < 0.01 vs the corresponding value of control rats.
Figure 2
Figure 2
mRNA concentrations for genes involved in fatty acid synthesis (FAS, ACC1, Srebp-1c, ChREBP) and in uptake of fatty acids from plasma lipids (FAT, LPL, VLDLr) in aortas of control (CO) and ZO rats studied at the age of 7, 14 and 21 weeks. * p < 0.05 vs the corresponding value of control rats.
Figure 3
Figure 3
Expression of lipogenic genes in the liver of 14 week old control (CO) and obese (ZO) Zucker rats. * p < 0.05, ** p < 0.01, *** p < 0.001 vs values in CO rats.
Figure 4
Figure 4
Concentrations of mRNA for lipogenic genes measured in human atheroma plaques (A) and in adjacent macroscopically intact tissue (MIT). Samples were collected during carotid endarterectomy in diabetic (n = 6) or non diabetic (n = 6) subjects. * p < 0.05 vs values in the MIT of the same subjects; £ p < 0.05 vs the corresponding value of non diabetic subjects.
Figure 5
Figure 5
Lipogenic mRNA concentrations measured in the basal state in cultured VSMC obtained from aortas of Zucker obese (ZO) and control (CO) rats. ** p < 0.01 vs the value of controls.
Figure 6
Figure 6
Srebp-1c and ChREBP mRNA concentrations in cultured VSMC of Zucker obese (ZO) and control (CO) rats. Concentrations were measured in the basal state (D0, glucose 5 mM) and after 3, 7 and 21 days of culture (D3, D7, D21) in basal conditions (glucose 5 mM), in presence of raised glucose concentration (25 mM) or in the presence of adipogenic differentiation medium (ADM) without or with raised glucose concentrations. * p < 0.05, ** p < 0.01 vs the value observed at T0; £ p < 0.05, ££ p < 0.01, £££ p < 0.001 vs the corresponding value of VSMC of control rats.
Figure 7
Figure 7
FAS and ACC1 mRNA concentrations in cultured VSMC of Zucker obese (ZO) and control (CO) rats. Concentrations were measured in the basal state (D0, glucose 5 mM) and after 3, 7 and 21 days of culture (D3, D7, D21) in basal conditions (glucose 5 mM), in presence of raised glucose concentration (25 mM) or in the presence of adipogenic differentiation medium (ADM) without or with raised glucose concentrations. * p < 0.05, ** p < 0.01 vs the value observed at T0; £ p < 0.05, ££ p < 0.01, £££ p < 0.001 vs the corresponding value of VSMC of control rats.
Figure 8
Figure 8
Activity of the lipogenic pathway (expressed as contribution to the cellular TG pool) measured in VSMC of control and obese Zucker rats cultured in the presence or absence of adipogenic medium (ADM) (panel A), in the presence or absence of insulin, trioiodothyronine (T3) or angiotensin II (AngII) (panel B) and in VSMC of control Zucker rats cultured without (control) or with TO901317 (TO) or PCN (panel C). * p < 0.05, ** p < 0.01 vs the corresponding control situation.
Figure 9
Figure 9
FAS mRNA concentrations in VSMC of Zucker obese and control rats after three or seven days of culture in the absence (-) or presence (+) of insulin, T3 or angiotensin II. * p < 0.05, ** p < 0.01 vs the corresponding value in the absence (-) of the tested molecule.
Figure 10
Figure 10
Response of lipogenic genes to agonists of PXR (PCN), LXR (paxillin) and to a dual PXR and LXR agonist (TO901317). mRNA concentrations (VSMC of control rats) were measured after three days of culture (glucose 5 mM, no ADM) in the absence (control) or presence of the various agonists. * p < 0.05, ** p < 0.01, ***p < 0.001 vs control.
Figure 11
Figure 11
Expression of lipogenic genes in liver (upper panel) and aortas (lower panel) of mice after a three days administration of GW3965 (black columns) or vehicle alone (control, white columns). * p < 0.05 vs the control group.
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References

    1. Schaffer J. Lipotoxicity: when tissues overeat. Curr Opin Lipidol. 2003;14:281–287. doi: 10.1097/00041433-200306000-00008. - DOI - PubMed
    1. Schulman G. Cellular mechanisms of insulin resistance. J Clin Invest. 2000;106:171–176. doi: 10.1172/JCI10583. - DOI - PMC - PubMed
    1. Capeau J. Insulin resistance and steatosis in humans. Diabetes Metab. 2008;34:649–657. doi: 10.1016/S1262-3636(08)74600-7. - DOI - PubMed
    1. Schrauwen P. High-fat diet, muscular lipotoxicity and insulin resistance. Proc Nutr Soc. 2007;66:33–41. doi: 10.1017/S0029665107005277. - DOI - PubMed
    1. Listenberger L, Han X, Lewis S, Cases S, Farese R, Ory D, Schaffer J. Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc Natl Acad Sci. 2003;100:3077–3082. doi: 10.1073/pnas.0630588100. - DOI - PMC - PubMed

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