Inflamación y síndrome metabólico por resistencia a la insulina-leptina en pacientes con psoriasis / Inflammation and metabolic syndrome due to insulin-leptin resistance in psoriatic patients

Resumen La psoriasis es una enfermedad inflamatoria crónica que se distingue por hiperproliferación recidivante de la piel, de causa y patogénesis multifactoriales. Afecta aproximadamente a 1-3% de la población en general. Durante los últimos diez años, en diversos estudios se ha encontrado que los pacientes con psoriasis tienen prevalencia elevada de factores de riesgo cardiovascular. Asimismo, esos estudios también sugieren una relación entre el síndrome metabólico y la psoriasis. El síndrome metabólico comprende una serie de condiciones fisiopatológicas relacionadas principalmente con aspectos metabólicos, como la resistencia y señalización a la insulina y leptina (Sx Met_RI-Lep). Es un grupo de factores de riesgo que incluye obesidad central, dislipidemia aterogénica, hipertensión arterial sistémica e intolerancia a la glucosa. Su importancia se debe a que duplica el riesgo de enfermedad cardiovascular y diabetes mellitus tipo 2, y aumenta la mortalidad incluso más que sus componentes por separado. La prevalencia mundial del síndrome varía en función del país y de los criterios utilizados para medirla; varía entre 15 y 47% de la población general. Las prevalencias publicadas también varían de acuerdo con las organizaciones que las emiten; tal es el caso de los criterios de la Organización Mundial de la Salud (OMS), que indican que la prevalencia en México es de 14%, y al aplicar los criterios ATP-III asciende a 27%. Existen, por tanto, 6.7 y 14.3 millones de mexicanos afectados, según los criterios de la Organización Mundial de la Salud y los ATP-III, respectivamente. La asociación de la psoriasis con otras enfermedades sistémicas podría deberse a diversas causas, como predisposición genética, factores ambientales (tabaco, alcohol, vida sedentaria) o tratamientos sistémicos prescritos. Cada vez son más los estudios que relacionan el síndrome metabólico por resistencia a la insulina-leptina con la psoriasis. En esta revisión bibliográfica se pretende sintetizar los mecanismos fisiopatológicos compartidos por ambos padecimientos, así como insistir en el cribado de los factores de riesgo cardiovasculares y del síndrome metabólico para prevenir o mejorar el tratamiento y pronóstico de los pacientes con psoriasis.

Abstract Psoriasis is a chronic inflammatory disease characterized by relapsing skin hyperproliferation, with multifactorial pathogenesis and causes. It affects approximately 1% to 3% of the general population. During the past ten years, several studies have found that patients with psoriasis have a high prevalence of cardiovascular risk factors. Likewise, such studies also suggest a link between metabolic syndrome and psoriasis. Metabolic syndrome comprises a number of pathophysiologic conditions that mainly involves the metabolic aspects concerning insulin-leptin resistance and signaling (Sx Met_RI-Lep). It is a group of risk factors including central obesity, atherogenic dyslipidemia, systemic hypertension and glucose intolerance. Its importance is due to its presence doubles the risk of cardiovascular disease, type 2 diabetes mellitus and increases mortality higher than its separate components. The worldwide prevalence of the syndrome varies depending on the country and the criteria used; between 15% and 47% of the general population. The prevalence published also vary according to the organizations that issue; such is the case of the criteria of the World Health Organization (WHO) to handle a prevalence in Mexico of 14% and applying the criteria ATP-III rises to 27%, so there are 6.7 and 14.3 million Mexicans affected, according to the criteria of the World Health Organization and the ATP-III, respectively. The association of psoriasis with other systemic diseases may be due to various causes such as genetic predisposition, environmental factors (smoking, alcohol, sedentary lifestyle) or be influenced by systemic treatments used against psoriasis. More and more studies link the Sx Met_RI-Lep with psoriasis. This paper summarizes the pathophysiological mechanisms shared by both pathologies, as well as emphasizes screening for cardiovascular risk factors and metabolic syndrome to improve treatment and prognosis of psoriasis.

Effect of Shengqing Herbs on Leptin Resistance of Diet-Induced Obesity Rats / 中国中医药信息杂志

Objective To observe the effects of Shengqing Chinese herbs on the obesity and leptin resistance of diet-induced obesity (DIO) rats.Methods Wistar rats were produced a rat model including of 40 DIO rats and 10 DIO-R rats. The DIO rats were divided into DIO model group, sibutramine group, Jianpi Liqi group and Shengqing group, which were respectively by gavage of saline, sibutramine, Jianpi Liqi herbs (Citri reticulatae pericarpium, Aucklandiae radix, Aurantii fructus immaturus), Shengqing herbs (Bupleuri radix, Cimicifugae rhizoma, Puerariae lobatae radix), blank control group and DIO-R group were by gavage of saline. Their weight, were examined after 16 weeks gavage. Leptin and neuropeptide Y in the serum were examined. Leptin, TNF-α, and suppressors of cytokine signaling-3 (SOCS-3) in the homogenized fat were examined. Results Compared with the DIO-R group, DIO model group's body weight, NPY significantly increased (P<0.01);leptin in the serum and homogenized fat decreased (P<0.05);SOCS-3 increased (P<0.05). After drug intervention, weight of each drug group declined. Compared with the DIO model group, Jianpi Liqi group's leptin in the homogenized fat increased (P<0.05). Shengqing group's leptin in homogenized fat increased, body weight reduced, NPY and SOCS-3 levels decreased, and better than sibutramine group and Jianpi Liqi group (P<0.05,P<0.01).Conclusion Shengqing herbs can reduce obesity and inhibit leptin resistance.

The correlation research progress between leptin and senile osteoporosis / 医学研究生学报

Osteoporosis is a kind of systemic metabolic bone diseases ,characterized by bone loss , bone subtle structural dam-age.Leptin is a peptide hormone which secreted by fat cells , that has both positive and negative effects to the bone , and plays a role of regulating on bone metabolism .In vitro, Leptin can regulate proliferation of osteoblast and inhibit reabsorption of osteoblasts depend on osteoclast.In vivo, Leptin can inhibit the synthesis of serotonin in the brain stem and increase the sympathetic nerve signals output by the hypothalamus to the bone , it mainly has a negative effect .But clinical trials about the correlation between Leptin and senile oste-oporosis, the role of Leptin in the central nervous system and peripheral tissue problems are still unclear .In this paper, we will make a comprehensive overview about the latest research progress in the correlation between leptin and senile osteoporosis .

Role of Reactive Oxygen Species in Hypothalamic Regulation of Energy Metabolism

To understand the etiology of metabolic disorders, including obesity and type II diabetes, it is essential to gain better insight into how stored and available energy sources are monitored by the central nervous system. In particular, a comprehension of the fine cellular interplay and intracellular mechanisms that enable appropriate hypothalamic and consequent endocrine and behavioral responses to both circulating hormonal and nutrient signals remains elusive. Recent data, including those from our laboratories, raised the notion that reactive oxygen species (ROS) generation is not merely a by-product of substrate oxidation, but it plays a crucial role in modulating cellular responses involved in the regulation of energy metabolism. These review summarizes the published recent data on the effect of ROS levels in the regulation of neuronal function, including that of hypothalamic melanocortin neurons, pro-opiomelanocortin and neuropeptide Y-/agouti related peptide-neurons, in the modulation of food intake.

Improvement of Leptin Resistance / 영남의대학술지

Leptin, a 16-kDa cytokine, is secreted by adipose tissue in response to the surplus of fat store. Thereby, the brain is informed about the body's energy status. In the hypothalamus, leptin triggers specific neuronal subpopulations (e.g., POMC and NPY neurons) and activates several intracellular signaling events, including the JAK/STAT, MAPK, PI3K, and mTOR pathway, which eventually translates into decreased food intake and increased energy expenditure. Leptin signal is inhibited by a feedback inhibitory pathway mediated by SOCS3. PTP1B involves another inhibitory pathway of leptin. Leptin potently promotes fat mass loss and body weight reduction in lean subjects. However, it is not widely used in the clinical field because of leptin resistance, which is a common feature of obesity characterized by hyperleptinemia and the failure of exogenous leptin administration to provide therapeutic benefit in rodents and humans. The potential mechanisms of leptin resistance include the following: 1) increases in circulating leptin-binding proteins, 2) reduced transport of leptin across the blood-brain barrier, 3) decreased leptin receptor-B (LRB), and/or 4) the provocation of processes that diminish cellular leptin signaling (inflammation, endoplasmic reticulum stress, feedback inhibition, etc.). Thus, interference of the cellular mechanisms that attenuate leptin signaling improves leptin action in cells and animal models, suggesting the potential utility of these processes as points of therapeutic intervention. Various experimental trials and compounds that improve leptin resistance are introduced in this paper.

Dieta hiperlipídica materna, tecido adiposo, fígado, metabolismo de carboidratos e sinalização central de leptina na prole de camundongos C57BL/6 / Maternal high-fat diet, adipose tissue, liver, carbohydrate metabolism and central signaling of leptin in the offspring of C57BL/6 mice

O consumo materno de dieta hiperlipídica saturada durante a gestação e lactação favorece o desenvolvimento obesidade e anormalidades metabólicas na prole. Este trabalho teve como objetivo testar a hipótese de que a prole proveniente de mães alimentadas com dieta hiperlipídica durante a gestação e lactação desenvolve obesidade e anormalidades metabólicas e de que essas alterações estão associadas a resistência central a leptina. As ratas grávidas da linhagem C57BL/6 (n=20) foram alimentadas com dieta standard chow (SC; 19% de lipídeos) ou dieta hiperlipídica (HF; 49% de lipídeos) durante todo período de gestação e lactação. Após o desmame, a prole de machos foi dividida em quatro grupos experimentais, de acordo com a dieta das mães e da prole: SC(mães)/SC(prole), SC/HF, HF/SC e HF/HF (n=12/gp). As características metabólicas foram avaliadas pela curva de ganho de peso; medida da pressão arterial; glicose de jejum, área sob a curva no teste oral de tolerância a glicose; concentrações de triglicerídeos hepáticos e estimativa da esteatose hepática; análise plasmática de insulina e leptina e; distribuição e análise morfológica do tecido adiposo. Para analisar a sensibilidade a leptina, os quatro grupos originais foram subdivididos em dois grupos cada (veículo ou leptina-5µg) para verificar a resposta alimentar (g) após o tratamento agudo intracerebroventricular (ICV) e a sinalização hipotalâmica de leptina. A dieta HF durante o período pós-desmame (grupo SC/HF), durante gestação e lactação (grupo HF/SC), ou ambos os períodos (grupo HF/HF), promoveu aumento da massa corporal. No que concerne as alterações hepáticas e a ação da insulina, a dieta HF durante o período perinatal favoreceu 25% de esteatose hepática, hiperinsulinemia e hiperleptinemia, enquanto os demais grupos experimentais SC/HF e HF/HF, demonstraram um padrão mais exacerbado...

Maternal high-fat diet consumption during pregnancy and lactation causes metabolic abnormalities (MA) (similar to metabolic syndrome in humans) in the rodents’ offspring. We tested the hypothesis that the offspring of dams fed a high fat diet during pregnancy and lactation develop MA and leptin resistance.Pregnant C57BL6 mice (n=20) were fed either standard chow (SC; 19% fat) or a high fat diet (HF; 49% fat). After weaning, male offspring were divided into four groups according to the diet of dams and offspring: SC(dams)/SC(offspring), SC/HF, HF/SC and HF/HF (n=12/group). MA were characterized by weight gain curve measured weekly; tail-cuff systolic pressure; fast glucose and areas under the curve after oral glucose tolerance test; fat mass depots; leptin and insulin concentrations, all performed at 12 weeks of age.To analyze leptin sensitivity, each group was divided into two groups (vehicle or leptin-5µg) to identify the feeding response and pSTAT3 expression after acute intracerebroventricular (ICV) treatment (n=6/group). The HF schedule during post-weaning (SC/HF group), during gestation and lactation (HF/SC group), or both periods (HF/HF group), increased body mass in experimental groups. In respect to hepatic alterations and insulin action, the HF diet during gestation and lactation caused 25% of liver steatosis, hiperinsulinemia and hiperleptinemia, whereas SC/HF and HF/HF presented worst patterns. The fat distribution and morphometry pointed for the key role of HF during gestation and lactation in amplify the ability to store fat in the offspring...

Effect of Shugan Huoxue Huatan Decoction on Insulin Resistance in Rats with Non-alcoholic Steatohepatitis / 中国中医药信息杂志

Objective To investigate the effects of Shugan Huoxue Huatan Decoction (SHHD) on non-alcoholic steatohepatitis (NASH) of rats. Methods 32 SD male rats were randomly allocated into 4 groups:normal group, model group, Dongbao Gantai (DBG) group, SHHD group. NASH model was induced by hyperlipid diet. General condition and pathological changes of liver tissues were observed. Liver function, blood lipids, liver tissue Hyp and serum LEP were dectected. Fasting insulin resistance index (FIRI) was evaluated according to the levels of fasting blood glucose (FBG) and fasting serum insulin (FINS). Results Compared with model group, SHHD had the effects of improving liver function and blood lipids, decreasing liver tissue Hyp, LEP and FIRI siginificantly. Conclusion Inhibiting leptin and insulin resistances, enhancing the lipid metabolism are probably the main mechanisms of SHHD in preventing and treating NASH.

Metformin Enhances Leptin Sensitivity in Aged Rats

To evaluate whether metformin restores leptin sensitivity in aged rats with leptin resistance, we measured leptin sensitivity in aged (2 year old) and adult (5 month old) rats after 4 weeks of treatment with metformin (300 mg/kg/D, mixing in drinking water), by measuring food intake, body weight and visceral fat losing effects. Leptin (15microgram/D) was administered by intracerobroventricular (i.c.v.) infusion through osmotic minipump for 1 week. Metformin treatment decreased body weight and daily food intake in both adult and aged rats compared with their control rats, however, these effects were more prominent in aged rats than in adult rats. Anorexic and fat losing responses following i.c.v. leptin were attenuated in aged rats compared to adult rats. However, these responses of aged rats to leptin were restored by metformin treatment. Moreover, serum concentration of leptin in aged rats was significantly decreased by combined treatment with metformin and leptin. These results suggest that metformin enhances leptin sensitivity in aged rat model, and that combination therapy with metformin and leptin would be helpful for treatment of aging-associated obesity.

Studies on Lepfin resistance of metabolic syndrome / 医学研究生学报

Objective: To investigate Leptin resistance of patients with metabolic syndrome. Methods: 50 patients with metabolic syndrome and 30 health persons as control were investigated. Body mass index(BMI)、waist to hip ratio(WHR)、blood pressure(Bp) were recorded. Serum Leptin、plasma glucose、insulin、total cholesterol(TC)、triglyceride(TG)、high density lipoprotein cholesterol(HDL C)、low density lipoprotein cholesterol(LDL C)、lipoprotein(a) were determined,and HOMA IR was calculated. Results: Compared to controls, serum Leptin concentration was significantly higher in metabolic syndrome〔(23.82?15.63)?g/L vs (11.20?4.70)?g/L, P

Study on the insulin resistance and leptin resistance in women with polycystic ovary syndrome / 医学研究生学报

Objective:To study the insulin resistance and leptin resistance in women with polycystic ovary syndrome(PCOS).Methods:Body mass index(BMI),serum leptin,fasting blood glucose(FBG),fasting insulin(FINS),serum triglyceride,total cholesterol,high-density lipoprotein,low-density lipoprotein and insulin resistance index(HOMA-IR) were assessed in 30 normal women,30 simple obesity women and 41 PCOS women.Results:①The PCOS patients showed higher levels of BMI,serum leptin,FINS,HOMA-IR and low-density lipoprotein,and lower levels of high-density lipoprotein than that in normal control.Compared to simple obesity women,there only showed higher FINS level and lower BMI in PCOS women.②Serum leptin levels in PCOS patients were concerned with BMI、FINS、HOMA-IR and serum triglyceride levels.③There were no significant difference of the FINS and HOMA-IR between normal women and non obese PCOS women,but the obese PCOS women showed higher levels of FINS and HOMA-IR than that in simple obesity women;the serum leptin levels showed no significant difference between normal women and non-obese PCOS women,simple obesity women and obese PCOS women. Conclusion:PCOS patients may have insulin resistance and leptin resistance;There may have regulative effect between leptin resistance and insulin resistance in PCOS patients;There are direct relationship between insulin resistance and PCOS;The rise of serum leptin level in PCOS women may be the assident manifestation of obesity.