Insulin resistance does not play a major role in lipid and apolipoprotein profile in obese women

Background: Obesity is associated with increased atherogenesis through alterations in lipids, among other potential factors. Some of those abnormalities might be mediated by insulin resistance (IR). Aims: To compare lipid and apolipoprotein profile between lean and obese women; to evaluate the influence of IR on lipid and apolipoprotein profile, in obese women. Methods: We studied 112 obese and 100 normal-weight premenopausal women without known cardiovascular disease. Both groups were characterized for anthropometrics and a fasting blood sample was collected for assessment of glucose, insulin, triglycerides, cholesterol (total, LDL and HDL), and apolipoproteins A-I, A-II, B, C-II, C-III, and E; IR was assessed by the homeostatic model assessment (HOMA-IR). We compared lipids between obese and lean women; we looked for correlation of those levels with anthropometrics and IR (independently from anthropometrics) in obese women. Results: Obese women were characterized by mean age=34.6±8.3 years, BMI=43.6±7.9 kg/m2, waist circumference (Wc)=117.5±15.1 cm, and HOMA-IR=4.28±3.5. Lean women (age=34.2±8.3 years, BMI=21.4±1.7 kg/m2, Wc=71.7±5.8 cm, and HOMA-IR=1.21±0.76) presented with significantly lower levels of total cholesterol (P=0.001), LDL-cholesterol (P<0.001), and triglycerides (P<0.001); they presented higher levels of HDL-cholesterol (P<0.001), Apo A-I (P<0.001) and Apo A-II (P=0.037). HOMA-IR showed no significant association with apolipoproteins. HOMA-IR was inversely associated with HDL-cholesterol (P=0.048; r=−0.187) but that association disappeared when we adjusted for waist circumference. Only triglycerides were directly associated with HOMA-IR (P<0.001; r=0.343) independently from anthropometrics. Conclusion: We confirm that obese women present worst lipid and apolipoprotein profile. However, with the exception for triglycerides, insulin resistance per se does not play a major role in lipid and apolipoprotein abnormalities observed in obese women.

Perfil lipídico em estudantes do ensino superior: caracterização numa população de jovens

O perfil lipídico é condicionado por diversos fatores, entre os quais os estilos de vida, a prática de exercício físico e os hábitos alimentares. Com o presente estudo pretende‑se avaliar o perfil lipídico numa população de jovens e estudar a sua associação com o índice de massa corporal, com os estilos de vida e os hábitos alimentares. Com um estudo exploratório descritivo, transversal, foi determinado o perfil lipídico de 97 estudantes, voluntários, do ensino superior, com idades compreendidas entre os 18 e os 25 anos. O perfil lipídico foi determinado pelo doseamento do colesterol total e frações (HDL e LDL) e triglicéridos. Foi identificado o índice de massa corporal e hábitos e estilos de vida, recolhidos pela aplicação de um questionário validado. No presente estudo não se observou alteração significativa do perfil lipídico, do IMC nem com o total do score alimentar. Não se encontraram associações entre as alterações lipídicas e o género, sendo que, nos estudantes com hábitos tabágicos, a fração HDL se encontrava mais baixa. O baixo score alimentar não se encontra associado ao perfil lipídico, o mesmo não se verificando em relação à prática de exercício físico. Verificou‑se um perfil lipídico alterado em 44,4% dos participantes, média de colesterol de 198,04mg/dl, triglicéridos de 82,58mg/dl, que são valores elevados para esta faixa etária. Os resultados deste estudo indicam que esta população deve monitorizar os fatores de risco de modo a prevenir patologia do foro cardio e cerebrovascular. ABSTRACT - The lipid profile is conditioned by several factors including the styles of life, physical exercise and eating habits. The present study is to evaluate the lipid profile in a population of students in higher education, and study their association with body mass index, with the lifestyles and eating habits. A descriptive exploratory study, transversal, we determined the lipid profile of 97 students, volunteers, higher education, aged 18 to 25 years. The lipid profile was determined by assay of total cholesterol and fractions (HDL and LDL) and triglycerides. It identified the body mass index and habits and lifestyles, collected by applying a validated questionnaire. In the present study, no significant change in lipid profile, BMI, nor with the total food score. No associations were found between lipid disorders and gender, and smoking habits in the students with the HDL fraction was lower. The low food score is not associated with lipid profile, the same was not observed in relation to physical exercise. There is an altered lipid profile in 44.4% of participants, average 198.04mg/dl cholesterol, triglycerides 82.58mg/dl, which are high values for this age group. The results of this study indicate that this population is to monitor the risk factors to prevent cardiovascular and cerebrovascular diseases.

Cholesterol 24S-Hydroxylase overexpression inhibits the liver X receptor (LXR) pathway by activating small guanosine triphosphate-binding proteins (sGTPases) in neuronal cells

The neuronal-specific cholesterol 24S-hydroxylase (CYP46A1) is important for brain cholesterol elimination. Cyp46a1 null mice exhibit severe deficiencies in learning and hippocampal long-term potentiation, suggested to be caused by a decrease in isoprenoid intermediates of the mevalonate pathway. Conversely, transgenic mice overexpressing CYP46A1 show an improved cognitive function. These results raised the question of whether CYP46A1 expression can modulate the activity of proteins that are crucial for neuronal function, namely of isoprenylated small guanosine triphosphate-binding proteins (sGTPases). Our results show that CYP46A1 overexpression in SH-SY5Y neuroblastoma cells and in primary cultures of rat cortical neurons leads to an increase in 3-hydroxy-3-methyl-glutaryl-CoA reductase activity and to an overall increase in membrane levels of RhoA, Rac1, Cdc42 and Rab8. This increase is accompanied by a specific increase in RhoA activation. Interestingly, treatment with lovastatin or a geranylgeranyltransferase-I inhibitor abolished the CYP46A1 effect. The CYP46A1-mediated increase in sGTPases membrane abundance was confirmed in vivo, in membrane fractions obtained from transgenic mice overexpressing this enzyme. Moreover, CYP46A1 overexpression leads to a decrease in the liver X receptor (LXR) transcriptional activity and in the mRNA levels of ATP-binding cassette transporter 1, sub-family A, member 1 and apolipoprotein E. This effect was abolished by inhibition of prenylation or by co-transfection of a RhoA dominant-negative mutant. Our results suggest a novel regulatory axis in neurons; under conditions of membrane cholesterol reduction by increased CYP46A1 expression, neurons increase isoprenoid synthesis and sGTPase prenylation. This leads to a reduction in LXR activity, and consequently to a decrease in the expression of LXR target genes.