Hepatic lipid metabolism in adult rats using early weaning models: sex-related differences.

Non-pharmacological early weaning (NPEW) induces liver damage in male progeny at adulthood; however, pharmacological early weaning (PEW) does not cause this dysfunction. To elucidate this difference in liver dysfunction between these two models and determine the phenotype of female offspring, de novo lipogenesis, ß-oxidation, very low-density lipoprotein (VLDL) export, and gluconeogenesis in both sexes were investigated in the adult Wistar rats that were weaned after a normal period of lactation (control group) or early weaned either by restriction of access to the dams' teats (NPEW group) or by reduction of dams' milk production with bromocriptine (PEW group). The offspring received standard diet from weaning to euthanasia (PN180). NPEW males had higher plasma triglycerides and TyG index, liver triglycerides, and cholesterol by de novo lipogenesis, which leads to intracellular lipids accumulation. As expected, hepatic morphology was preserved in PEW males, but they showed increased liver triglycerides. The only molecular difference between PEW and NPEW males was in acetyl-CoA carboxylase-1 (ACC-1) and stearoyl-CoA desaturase-1 (SCD-1), which were lower in PEW animals. Both early weaning (EW) females had no changes in liver cholesterol and triglyceride contents, and the hepatic cytoarchitecture was preserved. The expression of microsomal triglyceride transfer protein was increased in both the female EW groups, which could constitute a protective factor. The changes in hepatic lipid metabolism in EW offspring were less marked in females. EW impacted in the hepatic cytoarchitecture only in NPEW males, which showed higher ACC-1 and SCD-1 when compared to the PEW group. As these enzymes are lipogenic, it could explain a worsened liver function in NPEW males.

In Utero Dexamethasone Exposure Exacerbates Hepatic Steatosis in Rats That Consume Fructose During Adulthood.

Distinct environmental insults might interact with fructose consumption and contribute to the development of metabolic disorders. To address whether in utero glucocorticoid exposure and fructose intake modulate metabolic responses, adult female Wistar rats were exposed to dexamethasone (DEX) during pregnancy, and the offspring were administered fructose at a later time. Briefly, dams received DEX during the third period of pregnancy, while control dams remained untreated. Offspring born to control and DEX-treated mothers were defined as CTL-off and DEX-off, respectively, while untreated animals were designated CTL-off-CTL and DEX-off-CTL. CLT-off and DEX-off treated with 10% fructose in the drinking water for 8 weeks are referred to as CTL-off-FRU and DEX-off-FRU. We found that fructose promoted glucose intolerance and whole-body gluconeogenesis in both CTL-off-FRU and DEX-off-FRU animals. On the other hand, hepatic lipid accumulation was significantly stimulated in DEX-off-FRU rats when compared to the CTL-off-FRU group. The DEX-off-FRU group also displayed impaired very-low-density lipoprotein (VLDL) production and reduced hepatic expression of apoB, mttp, and sec22b. DEX-off-FRU has lower hepatic levels of autophagy markers. Taken together, our results support the unprecedented notion that in utero glucocorticoid exposure exacerbates hepatic steatosis caused by fructose consumption later in life.

ARHGAP21 deficiency impairs hepatic lipid metabolism and improves insulin signaling in lean and obese mice.

ARHGAP21 is a Rho-GAP that controls GTPases activity in several tissues, but its role on liver lipid metabolism is unknown. Thus, to achieve the Rho-GAP role in the liver, control and ARHGAP21-haplodeficient mice were fed chow (Ctl and Het) or high-fat diet (Ctl-HFD and Het-HFD) for 12 weeks, and pyruvate and insulin tolerance tests, insulin signaling, liver glycogen and triglycerides content, gene and protein expression, and very-low-density lipoprotein secretion were measured. Het mice displayed reduced body weight and plasma triglycerides levels, and increased liver insulin signaling. Reduced gluconeogenesis and increased glycogen content were observed in Het-HFD mice. Gene and protein expression of microsomal triglyceride transfer protein were reduced in both Het mice, while the lipogenic genes SREBP-1c and ACC were increased. ARHGAP21 knockdown resulted in hepatic steatosis through increased hepatic lipogenesis activity coupled with decreases in CPT1a expression and very-low-density lipoprotein export. In conclusion, liver of ARHGAP21-haplodeficient mice are more insulin sensitive, associated with higher lipid synthesis and lower lipid export.

Replacement of soybean oil by fish oil increases cytosolic lipases activities in liver and adipose tissue from rats fed a high-carbohydrate diets.

Several studies have demonstrated that fish oil consumption improves metabolic syndrome and comorbidities, as insulin resistance, nonalcoholic fatty liver disease, dyslipidaemia and hypertension induced by high-fat diet ingestion. Previously, we demonstrated that administration of a fructose-rich diet to rats induces liver lipid accumulation, accompanied by a decrease in liver cytosolic lipases activities. In this study, the effect of replacement of soybean oil by fish oil in a high-fructose diet (FRUC, 60% fructose) for 8 weeks on lipid metabolism in liver and epididymal adipose tissue from rats was investigated. The interaction between fish oil and FRUC diet increased glucose tolerance and decreased serum levels of triacylglycerol (TAG), VLDL-TAG secretion and lipid droplet volume of hepatocytes. In addition, the fish oil supplementation increased the liver cytosolic lipases activities, independently of the type of carbohydrate ingested. Our results firmly establish the physiological regulation of liver cytosolic lipases to maintain lipid homeostasis in hepatocytes. In epididymal adipose tissue, the replacement of soybean oil by fish oil in FRUC diet did not change the tissue weight and lipoprotein lipase activity; however, there was increased basal and insulin-stimulated de novo lipogenesis and glucose uptake. Increased cytosolic lipases activities were observed, despite the decreased basal and isoproterenol-stimulated glycerol release to the incubation medium. These findings suggest that fish oil increases the glycerokinase activity and glycerol phosphorylation from endogenous TAG hydrolysis. Our findings are the first to show that the fish oil ingestion increases cytosolic lipases activities in liver and adipose tissue from rats treated with high-carbohydrate diets.

The effects of trans-fatty acids on TAG regulation in mice depend on dietary unsaturated fatty acids.

The aim of this study was to investigate the effects of trans-fatty acids (TFA) on liver and serum TAG regulation in mice fed diets containing different proportions of n-3, n-6 and n-9 unsaturated fatty acids (UFA) from olive (O), maize (C) or rapeseed (R) oils partially substituted or not with TFA (Ot, Ct and Rt, respectively). Male CF1 mice were fed (30 d) one of these diets. The effects of the partial substitution (1 %, w/w) of different UFA with TFA on the activity and expression of hepatic enzymes involved in lipogenesis and fatty acids oxidation were evaluated, as well as their transcription factor expressions. Some of the mechanisms involved in the serum TAG regulation, hepatic VLDL rich in TAG (VLDL-TAG) secretion rate and lipoprotein lipase (LPL) activity were assessed. In liver, TFA induced an increase in TAG content in the Ot and Rt groups, and this effect was associated with an imbalance between lipogenesis and ß-oxidation. In the Ot group, exacerbated lipogenesis may be one of the mechanisms responsible for the liver steatosis induced by TFA, whereas in Rt it has been related to a decreased ß-oxidation, compared with their respective controls. The enhanced hepatic VLDL-TAG secretion in the Ot and Rt groups was compensated with a differential removal of TAG by LPL enzyme in extrahepatic tissues, leading to unchanged serum TAG levels. In brief, the effects of low levels of TFA on liver and serum TAG regulation in mice depend on the dietary proportions of n-3, n-6 and n-9 UFA.

Role of HDL in neutralizing the VLDL effect on endothelial dysfunction.

OBJECTIVE: It has been reported that LDL inhibits endothelium-dependent relaxation (EDR) and that HDL can neutralize this effect. However, the atherogenic properties of VLDL have been so far difficult to demonstrate. Studies on VLDL are controversial, and nothing is known about the role of HDL on potential VLDL vascular actions. We examined the effect of human VLDLs on EDR, and the role of HDL in this system. METHODS: VLDL (n=14) and LDL (n=6) were isolated from volunteer subjects. Normal HDL was obtained from one healthy donor. VLDL ability to inhibit ACh-induced vasorelaxation (10(-9)-10(-5)mM) on aortic rings previously precontracted by noradrenaline (10(-8)mM) was measured in the presence and absence of HDL. RESULTS: ACh-induced maximal relaxation (R%) was mildly, but not significantly attenuated in the presence of VLDL (72±7%), while LDL caused a significant inhibition (60±10%, p<0.05) when compared to incubation in the absence of lipoproteins. VLDLs were subdivided into 2 groups depending on their cholesterol/triglyceride ratio: 0.18-0.22 (n=8) was considered typical and 0.10-0.15, rich in triglycerides (VLDLRT, n=6). Typical VLDL had no effect on EDR (p=0.38), however R% from VLDLRT was lower (54±7%, p<0.01) similar to the one obtained with LDL (p=0.32). HDL showed favorable effects on EDR inhibition induced by the presence of VLDLRT (p<0.05.). CONCLUSION: Although typical VLDL did not cause endothelial dysfunction, triglyceride-enriched VLDL had inhibitory effect on EDR. It is proposed that alterations in VLDL composition would increase its atherogenic capacity. Moreover HDL appears to protect endothelium from VLDL action.

Sucrose-rich feeding during rat pregnancy-lactation and/or after weaning alters glucose and lipid metabolism in adult offspring.

1. Adverse fetal and early life environments predispose to the development of metabolic disorders in adulthood. The present study examined whether offspring of normal Wistar dams fed a high-sucrose diet (SRD) developed impaired lipid and glucose homeostasis when fed a control diet (CD) after weaning. In addition, we investigated whether there were more pronounced derangements in lipid and glucose homeostasis when offspring of SRD-fed Wistar were fed an SRD after weaning compared with those in offspring of CD-fed dams weaned on an SRD. 2. During pregnancy and lactation, female rats were fed either an SRD or CD. After weaning, half the male offspring from both groups were fed a CD or SRD, up to 100 days of age (CD-CD, CD-SRD, SRD-SRD and SRD-CD groups). 3. Final bodyweight was similar between all groups, although offspring of SRD-fed dams had lighter bodyweight at birth. Plasma lipid and glucose levels were significantly higher (P < 0.05) without changes in insulin levels in the CD-SRD, SRD-SRD and SRD-CD groups compared with the CD-CD group. Dyslipidaemia in the CD-SRD and SRD-SRD groups resulted from increased secretion of very low-density lipoprotein triacylglycerol, as well as decreased triacylglycerol (TAG) clearance that was associated with increased liver TAG content (P < 0.05) compared with the CD-CD group. The hypertriglyceridaemia observed in the SRD-CD group was mostly associated with decreased TAG clearance. Altered glucose and insulin tolerance were observed when the SRD was fed during any period of life. 4. These data support the hypothesis that early life exposure to SRD is associated with changes in lipid and glucose metabolism, leading to an unfavourable profile in adulthood, regardless of whether offspring consumed an SRD after weaning.

Cholecystectomy increases hepatic triglyceride content and very-low-density lipoproteins production in mice.

BACKGROUND & AIMS: Bile acid (BA) pool size remains unchanged after cholecystectomy (XGB) but it circulates faster, exposing the enterohepatic system to an increased flux of BA. Triglyceride (TG) and BA metabolisms are functionally inter-related. We investigated whether ablation of the gallbladder (GB) modifies hepatic TG metabolism. METHODS: Male mice were subjected to XGB and fed a normal diet. In some experiments, mice received a 1% nicotinic acid diet to block lipolysis. Parameters of BA and TG metabolism, and microsomal triglyceride transfer protein (MTTP) activity were measured 1-2 months after XGB. Serum parameters, hepatic lipids and mRNA expression of genes of lipid metabolism were determined. RESULTS: BA pool size and synthesis were normal, but biliary BA secretion doubled during the diurnal light phase in XGB mice. Serum and hepatic TG concentrations increased 25% (P<0.02), and hepatic very-low-density lipoproteins (VLDL)-TG and apoB-48 productions increased 15% (P<0.03) and 50% (P<0.01), respectively, after XGB. Feeding a 1% nicotinic acid did normalize VLDL production. MTTP activity increased 15% (P<0.005) after XGB. Hepatic free fatty acid (FFA) synthesis and content, and mRNA levels of lipid metabolism-related genes remained normal in XGD mice. CONCLUSIONS: XGB increased serum and hepatic TG levels, and VLDL production, which were restored to normal by nicotinic acid. The results suggest that FFA flux from adipose tissue to the liver is increased in XGB mice. They support the hypothesis that the GB has a role in the regulation of hepatic TG metabolism and that XGB may favour the accumulation of fat in the liver.

Hepatic denervation impairs the assembly and secretion of VLDL-TAG.

VLDL secretion is a regulated process that depends on the availability of lipids, apoB and MTP. Our aim was to investigate the effect of liver denervation upon the secretion of VLDL and the expression of proteins involved in this process. Denervation was achieved by applying a 85% phenol solution onto the portal tract, while control animals were treated with 9% NaCl. VLDL secretion was evaluated by the Tyloxapol method. The hepatic concentration of TAG and cholesterol, and the plasma concentration of TAG, cholesterol, VLDL-TAG, VLDL-cholesterol and HDL-cholesterol were measured, as well as mRNA expression of proteins involved in the process of VLDL assembly. Hepatic acinar distribution of MTP and apoB was evaluated by immunohistochemistry. Denervation increased plasma concentration of cholesterol (125.3 +/- 10.1 vs. 67.1 +/- 4.9 mg dL(-1)) and VLDL-cholesterol (61.6 +/- 5.6 vs. 29.4 +/- 3.3 mg dL(-1)), but HDL-cholesterol was unchanged (45.5 +/- 6.1 vs. 36.9 +/- 3.9 mg dL(-1)). Secretion of VLDL-TAG (47.5 +/- 23.8 vs. 148.5 +/- 27.4 mg dL h(-1)) and mRNA expression of CPT I and apoB were reduced (p < 0.01) in the denervated animals. MTP and apoB acinar distribution was not altered in the denervated animals, but the intensity of the reaction was reduced in relation to controls.

CETP expression enhances liver HDL-cholesteryl ester uptake but does not alter VLDL and biliary lipid secretion.

The aim of this work was to study how CETP expression affects whole body cholesterol homeostasis. Thus, tissue uptake and plasma removal rates of labeled HDL-cholesteryl ester (CE), VLDL secretion rates, and biliary lipid secretion and fecal bile acid content were compared between human CETP transgenic (Tg) and non-transgenic (nTg) mice fed with a standard diet. CETP Tg mice exhibited increased HDL-CE plasma fractional catabolic rate and uptake by the liver, adrenals, adipose tissue and spleen. HDL fractions from both CETP Tg and from nTg mice were removed faster from the plasma of CETP expressing than from nTg mice, suggesting a direct role of CETP in accelerating tissue CE uptake. However, neither hepatic output of VLDL cholesterol and triglycerides nor biliary lipid and fecal bile acid excretion were changed in CETP Tg compared to nTg mice. CETP Tg mice also showed enhanced hepatic cholesterol content. Steady state cholesterol homeostasis was probably preserved through the downregulation of hepatic HMG-CoA reductase and LDL receptor expression. In conclusion, although CETP expression facilitates cholesteryl ester tissue uptake, it does not alter biliary lipid and fecal bile acid excretion, the mandatory final step of the reverse cholesterol transport.

Endogenous hypertriglyceridemia intensifies the course of cerulein-induced pancreatitis in rat: relation with changes in the VLDL composition.

AIMS: To study if the course of cerulein-induced pancreatitis in rats changes in a state of triglyceride-rich lipoprotein metabolism alteration. METHODS: Two groups of rats received control diet during a 90-day period (A) and sucrose-rich diet to induce endogenous hypertriglyceridemia (B). Subgroups A2 and B2 received i.p. 45 microg cerulein/kg body weight (to induce acute pancreatitis). Histological examination of pancreas tissue, serum pancreatic lipase, lipoprotein profile and VLDL chemical composition were assessed. Then, pancreatic lipase hydrolytic activity on VLDL-triglycerides was evaluated in vitro. RESULTS: Cellular vacuolization was observed in all of the cerulein-injected rats, but only in subgroup B2 fat necrosis was present. Serum triglycerides were higher in subgroup B1 than in subgroup A1 (mean +/- SEM, mg/dl 123,77 +/- 25.7 vs. 65.8 +/- 7, p < 0.01). Triglycerides from rats fed with sucrose-rich diet, decreased after cerulein-induced pancreatitis (80.38 +/- 11.3 vs. 123,77 +/- 25.7, p < 0.02). Moreover, the endogenous hypertriglyceridemic rats showed an increment of VLDL triglyceride content, which decreased when rats were injected with cerulein. A negative correlation was found between VLDL-triglyceride content and serum pancreatic lipase activity (r = 0.58, p < 0.02). The in vitro assay showed a decrease in VLDL-triglyceride content post incubation with pancreatic lipase enriched serum (mean +/- SD: 59.2 +/- 27.7%, p < 0.01). CONCLUSIONS: The endogenous hypertriglyceridemia intensifies the course of cerulein-induced pancreatitis and it could be related to the decrease in VLDL-triglycerides as a consequence of pancreatic lipase hydrolytic activity.

Hepatic overexpression of sterol carrier protein-2 inhibits VLDL production and reciprocally enhances biliary lipid secretion.

We examined in vivo a role for sterol carrier protein-2 (SCP-2) in the regulation of lipid secretion across the hepatic sinusoidal and canalicular membranes. Recombinant adenovirus Ad.rSCP2 was used to overexpress SCP-2 in livers of mice. We determined plasma, hepatic, and biliary lipid concentrations; hepatic fatty acid (FA) and cholesterol synthesis; hepatic and biliary phosphatidylcholine (PC) molecular species; and VLDL triglyceride production. In Ad.rSCP2 mice, there was marked inhibition of hepatic fatty acids and cholesterol synthesis to <62% of control mice. Hepatic triglyceride contents were decreased, while cholesterol and phospholipids concentrations were elevated in Ad.rSCP2 mice. Hepatic VLDL triglyceride production fell in Ad.rSCP2 mice to 39% of control values. As expected, biliary cholesterol, phospholipids, bile acids outputs, and biliary PC hydrophobic index were significantly increased in Ad.rSCP2 mice. These studies indicate that SCP-2 overexpression in the liver markedly inhibits lipid synthesis as well as VLDL production, and alters hepatic lipid contents. In contrast, SCP-2 increased biliary lipid secretion and the proportion of hydrophobic PC molecular species in bile. These effects suggest a key regulatory role for SCP-2 in hepatic lipid metabolism and the existence of a reciprocal relationship between the fluxes of lipids across the sinusoidal and canalicular membranes.

Kinetics of in vitro lipolysis of human very low-density lipoprotein by lipoprotein lipase.

BACKGROUND AND AIM: An initial step in the catabolism of triglyceride-rich lipoprotein involves the hydrolysis of the triglyceride moiety by lipoprotein lipase (LPL). As differences in the lipolytic behaviour of very low-density lipoprotein (VLDL) particles have been observed, it is possible that different VLDL particles have a different affinity to the enzyme, which means that their fate may partially depend on the LPL-mediated hydrolysis of their triglyceride content. Our aim was to determine whether variation in VLDL chemical composition affects their properties as a substrate for LPL. METHODS AND RESULTS: Isolated VLDL was incubated in vitro with bovine LPL to determine substrate affinity. Under optimal assay conditions, free fatty acids were measured and the kinetic indicators for in vitro triglyceride hydrolysis (Km and Vmax) were calculated. VLDL cholesterol (VLDL-C), VLDL-apoB and the cholesterol/triglyceride ratio were assessed and the triglyceride/protein and triglyceride/apoB ratios were calculated as lipoprotein size estimators. VLDL-C, VLDL-apoB and the VLDL-C/triglyceride ratio positively correlated with Km: r = 0.52, p < 0.01; r = 0.52, p < 0.03; r = 0.69, p < 0.001 respectively. No correlation was found between the VLDL-triglyceride/protein or the VLDL-triglyceride/apoB ratios and Km (r = -0.20, and -0.06 respectively, p = not significant). Of the subjects' anthropometric characteristics, only the waist/hip ratio significantly correlated with Km: r = 0.63, p < 0.01. CONCLUSIONS: In the present study, we investigated the substrate function of VLDL particles in vitro. Enzyme affinity seems to be associated with cholesterol-triglyceride content or the number of VLDL particles rather than particle size. It may be expected that VLDL with a low cholesterol/triglyceride ratio will be efficiently lypolised by LPL, thus leading to the formation of a smaller particle with atherogenic potential.

Increased lipogenesis and resistance of lipoproteins to oxidative modification in two patients with glycogen storage disease type 1a.

We describe 2 patients with glycogen storage disease type 1a and severe hyperlipidemia without premature atherosclerosis. Susceptibility of low-density lipoproteins to oxidation was decreased, possibly related to the ~40-fold increase in palmitate synthesis altering lipoprotein saturated fatty acid contents. These findings are potentially relevant for antihyperlipidemic treatment in patients with glycogen storage disease type 1a.

Changes in the profile of lipoprotein subfractions associated with hormone replacement therapy.

OBJECTIVE: To report the effects of 2 regimens of hormone replacement therapy during the postmenopausal period on the profile of the major lipoprotein subfractions (HDL, LDL, and VLDL). METHODS: We carried out a cohort study in 38 postmenopausal patients who were starting their hormone replacement therapy due to gynecological indications, for a period of 12 weeks. Analysis of lipoprotein subclasses was performed through nuclear magnetic resonance spectroscopy. RESULTS: Hormone replacement therapy cause an increase in the proportion of larger subfractions of VLDL and HDL (p=0.008 and 0.03, respectively) and in the proportion of larger particles of VLDL due to a 36% increase in the levels of larger particles (p=0.004), concomitantly with a 15% reduction in the levels of smaller particles (p=0.04). In regard to HDL, the increase occurred only a 17% increase in the levels of larger particles (p=0.002). No significant change occurred in the distribution pattern of LDL subfractions. CONCLUSION: The proportion of larger subfractions of VLDL and HDL increases after hormone replacement therapy. The increase in the proportion of larger particles of VLDL occurs due to an increase in the levels of the larger subclasses concomitantly with a reduction in the smaller particles. However, an increase in the proportion of larger particles of HDL occurs only due to an increase in the levels of the larger subfractions.

Alteraçöes do perfil das subfraçöes de lipoproteínas associadas à terapia de reposiçäo hormonal / Changes in the profile of lipoprotein subfractions associated with hormone replacement therapy

OBJECTIVE: To report the effects of 2 regimens of hormone replacement therapy during the postmenopausal period on the profile of the major lipoprotein subfractions (HDL, LDL, and VLDL). METHODS: We carried out a cohort study in 38 postmenopausal patients who were starting their hormone replacement therapy due to gynecological indications, for a period of 12 weeks. Analysis of lipoprotein subclasses was performed through nuclear magnetic resonance spectroscopy. RESULTS: Hormone replacement therapy cause an increase in the proportion of larger subfractions of VLDL and HDL (p=0.008 and 0.03, respectively) and in the proportion of larger particles of VLDL due to a 36 percent increase in the levels of larger particles (p=0.004), concomitantly with a 15 percent reduction in the levels of smaller particles (p=0.04). In regard to HDL, the increase occurred only a 17 percent increase in the levels of larger particles (p=0.002). No significant change occurred in the distribution pattern of LDL subfractions. CONCLUSION: The proportion of larger subfractions of VLDL and HDL increases after hormone replacement therapy. The increase in the proportion of larger particles of VLDL occurs due to an increase in the levels of the larger subclasses concomitantly with a reduction in the smaller particles. However, an increase in the proportion of larger particles of HDL occurs only due to an increase in the levels of the larger subfractions

[Lipoprotein glycation and glycoxidation: their importance in diabetes mellitus]. / La glicación y glicoxidación de las lipoproteínas. Su importancia en la diabetes mellitus.

Chronic hyperglycemia induces an increase in the non enzymatic glycation of circulating and structural proteins together with a glucose-generated oxidative and carbonyl stress, known as glycoxidation. The physicochemical characteristics and the metabolism of lipoproteins are altered by glycation/glycoxidation and resemble those of other body proteins, except for the fact that there is a simultaneous glycoxidation of both protein and phospholipid components generating an oxidative stress that increases lipoxidation. Information gathered during the last few years suggests that, among lipoproteins, modified LDL would principally contribute to developing diabetic micro-macrovascular complications. The control and the prevention of the progress of such complications are difficult to attain due to the irreversibility of glycoxidation. As glycation/glycoxidation is related to mean blood glucose, the goal in diabetes treatment must be the achievement of a close to normal metabolic control. This review summarizes advances in the importance of lipoprotein glycation/glycoxidation in diabetes mellitus.

La glicacion y glicoxidacion de las lipoproteinas: su importancia en la diabetes mellitus / Lipotrotein glyication and glycoxidation: their importance in diabetes mellitus

La hiperglucemia crónica produce un incremento en nivel de glicación no enzimática de proteínas estructurales y circulantes del organismo generando simultáneamente un estrés oxidativo (producción de radicales libres del oxígeno) y carbonílico, proceso denominado glicoxidación. Se ha demostrado que las diferentes lipoproteínas (LP) plasmáticas son afectadas por la glicación y/o glicoxidación produciéndose en ellas modificaciones fisicoquímicas y alteraciones en su metabolismo. La glicoxidación de las LP adquiere características particulares, con respecto a otras proteínas, por producirse al mismo tiempo en la porción proteica así como en los fosfolípidios que contienen, y generar un estrés oxidativo que favorecería la lipoxidación. Evidencias acumuladas en los últimos años sugieren que los cambios generados especialmente en las LDL que han sido las LP más estudiadas, podrían ser en parte responsables del desarrollo de la micro-macrovasculopatía diabética. Este tipo de complicaciones, una vez establecido es de difícil control y su progresión muchas veces inevitable por las características de irreversibilidad de los procesos de glicoxidación. Por lo tanto, y teniendo en cuenta que la glicación y/o glicoxidación dependen de los niveles promedio de glucosa circulante, la meta principal del tratamiento de las personas con diabetes deberá ser el mantenimiento de dichos promedios en valores lo más cercanos posibles a los de personas sin diabetes. Este trabajo resume los últimos adelantos en la glicaión-glicoxidación de las LP y su importancia en la diabetes melitus para información del profesional no especializado en el tema.

La glicacion y glicoxidacion de las lipoproteinas: su importancia en la diabetes mellitus / Lipotrotein glyication and glycoxidation: their importance in diabetes mellitus

La hiperglucemia crónica produce un incremento en nivel de glicación no enzimática de proteínas estructurales y circulantes del organismo generando simultáneamente un estrés oxidativo (producción de radicales libres del oxígeno) y carbonílico, proceso denominado glicoxidación. Se ha demostrado que las diferentes lipoproteínas (LP) plasmáticas son afectadas por la glicación y/o glicoxidación produciéndose en ellas modificaciones fisicoquímicas y alteraciones en su metabolismo. La glicoxidación de las LP adquiere características particulares, con respecto a otras proteínas, por producirse al mismo tiempo en la porción proteica así como en los fosfolípidios que contienen, y generar un estrés oxidativo que favorecería la lipoxidación. Evidencias acumuladas en los últimos años sugieren que los cambios generados especialmente en las LDL que han sido las LP más estudiadas, podrían ser en parte responsables del desarrollo de la micro-macrovasculopatía diabética. Este tipo de complicaciones, una vez establecido es de difícil control y su progresión muchas veces inevitable por las características de irreversibilidad de los procesos de glicoxidación. Por lo tanto, y teniendo en cuenta que la glicación y/o glicoxidación dependen de los niveles promedio de glucosa circulante, la meta principal del tratamiento de las personas con diabetes deberá ser el mantenimiento de dichos promedios en valores lo más cercanos posibles a los de personas sin diabetes. Este trabajo resume los últimos adelantos en la glicaión-glicoxidación de las LP y su importancia en la diabetes melitus para información del profesional no especializado en el tema. (Au)