Rol del enterocito en la dislipidemia de la diabetes mellitus tipo 2 / Role of the enterocyte in type 2 diabetes mellitus associated dyslipidemia

En la diabetes mellitus tipo 2 el aumento en la producción de quilomicrón en el estado post-prandial se asocia a mayor riesgo cardiovascular. La evidencia actual posiciona al enterocito como actor principal en la dislipemia de la diabetes mellitus tipo 2 debido a que aumenta la producción de apolipoproteína B-48 en respuesta a una elevación de ácidos grasos libres y glucosa. El metabolismo del quilomicrón se encuentra regulado por múltiples factores independientes además de la ingesta de grasa alimentaria. Entre estos factores se destacan las hormonas intestinales, como el péptido similar al glucagón tipo 1 que disminuye la producción de apolipoproteína B-48 y el péptido similar al glucagón tipo 2 que la aumenta. Por otro lado, la insulina inhibe de forma aguda la producción de quilomicrón en el sujeto sano mientras que en la diabetes mellitus tipo 2, este efecto está ausente. La comprensión de los factores reguladores emergentes de la secreción de quilomicrón permite vislumbrar nuevos mecanismos de control en su metabolismo y aportar estrategias terapéuticas focalizadas en la hiperlipidemia posprandial en la diabetes mellitus tipo 2 con la reducción del riesgo cardiovascular.

In type 2 diabetes mellitus there is an overproduction of chylomicron in the postprandial state that is associated with increased cardiovascular risk. Current evidence points out a leading role of enterocyte in dyslipidemia of type 2 diabetes mellitus, since it increases the production of apolipoprotein B-48 in response to a raise in plasma free fatty acids and glucose. The chylomicron metabolism is regulated by many factors apart from ingested fat, including hormonal and metabolic elements. More recently, studies about the role of gut hormones, have demonstrated that glucagon-like peptide-1 decreases the production of apolipoprotein B-48 and glucagon-like peptide-2 enhances it. Insulin acutely inhibits intestinal chylomicron production in healthy humans, whereas this acute inhibitory effect on apolipoprotein B-48 production is blunted in type 2 diabetes mellitus. Understanding these emerging regulators of intestinal chylomicron secretion may offer new mechanisms of control for its metabolism and provide novel therapeutic strategies focalized in type 2 diabetes mellitus postprandial hyperlipidemia with the reduction of cardiovascular disease risk.

Lipolysis of emulsion models of triglyceride-rich lipoproteins is altered in male patients with abdominal aorta aneurysm

Disorders of the lipid metabolism may play a role in the genesis of abdominal aorta aneurysm. The present study examined the intravascular catabolism of chylomicrons, the lipoproteins that carry the dietary lipids absorbed by the intestine in the circulation in patients with abdominal aorta aneurysm. Thirteen male patients (72 ± 5 years) with abdominal aorta aneurysm with normal plasma lipid profile and 13 healthy male control subjects (73 ± 5 years) participated in the study. The method of chylomicron-like emulsions was used to evaluate this metabolism. The emulsion labeled with 14C-cholesteryl oleate and ³H-triolein was injected intravenously in both groups. Blood samples were taken at regular intervals over 60 min to determine the decay curves. The fractional clearance rate (FCR) of the radioactive labels was calculated by compartmental analysis. The FCR of the emulsion with ³H-triolein was smaller in the aortic aneurysm patients than in controls (0.025 ± 0.017 vs 0.039 ± 0.019 min-1; P < 0.05), but the FCR of14C-cholesteryl oleate of both groups did not differ. In conclusion, as indicated by the triglyceride FCR, chylomicron lipolysis is diminished in male patients with aortic aneurysm, whereas the remnant removal which is traced by the cholesteryl oleate FCR is not altered. The results suggest that defects in the chylomicron metabolism may represent a risk factor for development of abdominal aortic aneurysm.

Metabolismo dos quilomícrons e capacidade da lipoproteína de alta densidade (HDL) de receber lípides na síndrome metabólica e no diabetes mellitus tipo 2 / Chylomicron metabolism and lipid reception capacity of high density lipoprotein in metabolic syndrome (MetS) and type 2 diabetes mellitus (DM2)

O principal distúrbio metabólico decorrente do Diabetes mellitus tipo 2 e da Síndrome Metabólica corresponde a alterações no metabolismo lipídico. Portanto, torna-se importante a melhor compreensão de alguns aspectos do metabolismo de lipoproteínas plasmáticas. Nesse sentido, a avaliação do metabolismo dos quilomícrons e da transferência de lípides de lipoproteínas plasmáticas para a lipoproteína de alta densidade (HDL), pode fornecer informações importantes relacionadas com o processo aterogênico. No presente estudo, foram estudados 15 indivíduos portadores de Diabetes mellitus tipo 2, 15 indivíduos com Síndrome Metabólica e 14 controles normolipidêmicos. Foi avaliada a cinética plasmática de uma nanoemulsão lipídica artificial com comportamento metabólico similar ao dos quilomícrons naturais, marcada com triglicérides (TG-3H) e éster de colesterol (EC-14C) radioativos. A nanoemulsão de quilomícrons artificiais foi injetada endovenosamente e amostras de sangue foram coletadas durante intervalos préestabelecidos. As curvas de decaimento plasmático dos lípides radioativos da nanoemulsão foram traçadas e as taxas fracionais de remoção (TFR) foram calculadas por análise compartimental. Para avaliação da transferência de lípides foi utilizada uma nanoemulsão semelhante a LDL (LDE) marcada com TG-3H e colesterol livre-14C (CL-14C) ou fosfolípides-14C (PL-14C) e EC-3H, como doadora de lípides para a HDL. Após incubação in vitro da LDE com o plasma, seguiu-se a precipitação das lipoproteínas que contem apolipoproteína B, restando no sobrenadante apenas a HDL. As taxas de transferência de lípides foram expressas em % de radioatividade encontrada no sobrenadante. Também foi determinado o diâmetro da HDL por espalhamento de luz. A TFR-EC dos grupos DM2 (p <0,05) e SM (p <0,01) comparado ao grupo controle apresentou-se diminuída, enquanto que as TFR-TG foram similares nos três grupos. Houve maior transferência de fosfolípides e colesterol nos grupos DM2 e SM...

The main metabolic disturbances occurring as a result of type 2 diabetes mellitus (DM2) and Metabolic Syndrome (MetS) are alterations in the metabolism of lipids. It is therefore, important to better understand the aspects by which plasma lipoproteins are metabolized. The evaluation of chylomicron metabolism and lipid transfer of high density lipoprotein (HDL) can thus yield useful information regarding the atherosclerotic process. In this study, 15 Type 2 Diabetes individuals, 15 Metabolic Syndrome individuals and 14 normolipidemic control individuals were studied. The plasmatic kinetics of an artificial lipidic nanoemulsion mimicking the behavior of natural chylomicrons were evaluated. This artificial chylomicron nanoemulsion, labele with radioactive triglycerides (TG-3H) and radioactive cholesteryl oleate (CO-14C) was injected intravenously and blood samples collected at pre-established time intervals. The plasmatic decay curve of the radioactive lipids of the nanoemulsion was traced and the fractional clearance rate calculated (FCR) through compartmental analysis. In order to evaluate the lipid transfer, we used a nanoemulsion similar to LDL., labeled with TG-3H and free cholesterol -14C (CL-14C) or with phospholipids -14C (PL-14C) and CO-3H, as a lipid donator to HDL. After in vitro nanoemulsion incubation with the plasma, the lipoproteins containing apolipoprotein B were precipitated, resulting in a supernatant containing HDL. The lipid transfer rates were expressed in % of radioactivity measured in the supernatant. It was also determined the diameter of the HDL using light scattering technique. The TFR-EC for the DM2 (p <0.05) and MetS (p <0.01) groups when compared to the control group was reduced. The TFR-TG, on the other hand, remained similar in all three groups. The transfer of phospholipids and cholesterol for the DM2 (p<0.001) and MetS groups was greater than that of the control group (p<0.001)...

Avaliação do metabolismo de quilomícrons artificiais em pacientes obesas e não obesas, portadoras da síndrome dos ovários policísticos / Evaluation of artificial chylomicrons metabolism in obese and nonobese patients with polycystic ovary syndrome

Este estudo teve como objetivos avaliar o metabolismo de quilomícrons utilizando a metodologia da cinética plasmática de uma emulsão de quilomícrons artificiais em pacientes com síndrome dos ovários policísticos (SOP), assim como o impacto da obesidade nesta cinética. Foram estudadas 43 mulheres adultas jovens, subdivididas em 4 grupos, sendo 8 pacientes com SOP e índice de massa corporal normal [SOP-N (IMC = 22,7 ± 1,9 Kg/m2)], e 15 com IMC >=30 kg/m2 [SOP-O (IMC = 33,8 ± 3,3 kg/m2)], pareadas com 20 mulheres controles, sendo 10 com IMC normal [Controle-N (IMC = 21 ± 1,76 kg/m2)] e 10 com IMC obeso [Controle-O (IMC = 33,7± 3,1 kg/m2)]. Quando os grupos foram comparados entre si, com relação às características antropométricas, perfil lipídico e apolipoproteínas; detectou-se diferença estatisticamente significante entre IMC (P < 0,001), circunferência abdominal (CA) (P < 0,001), colesterol total (P = 0,042), HDL-colesterol (P < 0,001), LDL-colesterol (P = 0,009), triglicérides (TG) (P < 0,001) e apolipoproteína B (P < 0,001). As médias destas variáveis foram maiores nos grupos Controle- O e SOP-O, não havendo diferenças entre eles. Com relação à apolipoproteína A1 e ácidos graxos livres não houve diferença entre os grupos. A média da apolipoproteína E foi significativamente maior no grupo Controle-N, não havendo diferença ao compararmos os outros três grupos entre si. Com relação à concentração dos hormônios, as pacientes com SOP tiveram médias significativamente maiores para a testosterona total e testosterona livre (TL) (P < 0,001, P = 0,001), respectivamente. O estradiol foi menor nas pacientes com SOP (P = 0,039), não havendo o impacto da obesidade nestas variáveis hormonais. A média da globulina ligadora dos esteróides (SHBG) foi significativamente maior no grupo Controle-N, não havendo diferença ao compararmos os outros três grupos entre si. Com relação ao modelo homeostático de resistência à insulina (HOMA-IR), houve um impacto significativo...

The aims of this study were to evaluate the chylomicrons metabolism using the method of plasma kinetics of an emulsion of artificial chylomicrons in patients with polycystic ovary syndrome (PCOS), as well as the impact of obesity in this kinetics. Forty-three young adult women were studied , subdivided into 4 groups: 8 of them, with PCOS and normal body mass index [ PCOS-N (BMI = 22.7 ± 1.9 kg/m2)], and 15 with BMI >=30 kg/m2 [PCOS-O (BMI = 33.8 ± 3.3 kg/m2 )] , pairwise matched with 20 controls, being 10 with normal BMI [ Control-N (BMI =21 ± 1.76 kg/m2 )] and 10 with obese BMI [Control-O (BMI = 33.7 ± 3.1 kg/m2 )]. When the groups were compared among themselves, in relation to the antropometric features, lipid profile and apolipoproteins; it was detected a statistically significant difference among BMI (P < 0.001), waist circunference (WC) (P < 0.001), total cholesterol (P = 0.042), HDL-cholesterol (P < 0.001), LDL-cholesterol (P = 0.009), triglycerides (TG) (P < 0.001) and apolipoprotein B (P < 0.001). The means of these variables were higher in the Control-O and PCOS groups and there were no differences among them. In relation to apolipoprotein A1 and to free fatty acids, there was no difference among the groups. The means of apolipoprotein E was significantly higher in the Control-N group and there was no difference when we compared the other three groups among themselves. In relation to hormone concentration, the PCOS patients had means significantly higher for total testosterone and free testosterone (P < 0.001, P = 0.001), respectively. Estradiol was lower in PCOS patients (P = 0.039), and there was no obesity impact in these hormonal variables. The means of sex hormone-binding globulin (SHBG) was significantly higher in the Control-N group, and there was no difference when we compared the other three groups among themselves. In relation to the homeostasis model assessment of insulin resistance (HOMA-IR), there was a significant impact of obesity...