Adiponectin, the adiponectin paradox, and Alzheimer's Disease: Is this association biologically plausible?

Dementia, especially Alzheimer's Disease (AD) and vascular dementia, is a major public health problem that continues to expand in both economically emerging and hegemonic countries. In 2017, the World Alzheimer Report estimated that over 50 million people were living with dementia globally. Metabolic dysfunctions of brain structures such as the hippocampus and cerebral cortex have been implicated as risk factors for dementia. Several well-defined metabolic risk factors for AD include visceral obesity, chronic inflammation, peripheral and brain insulin resistance, type 2 diabetes mellitus (T2DM), hypercholesterolemia, and others. In this review, we describe the relationship between the dysmetabolic mechanisms, although still unknown, and dementia, particularly AD. Adiponectin (ADPN), the most abundant circulating adipocytokine, acts as a protagonist in the metabolic dysfunction associated with AD, with unexpected and intriguing dual biological functions. This contradictory role of ADPN has been termed the adiponectin paradox. Some evidence suggests that the adiponectin paradox is important in amyloidogenic evolvability in AD. We present cumulative evidence showing that AD and T2DM share many common features. We also review the mechanistic pathways involving brain insulin resistance. We discuss the importance of the evolvability of amyloidogenic proteins (APs), defined as the capacity of a system for adaptive evolution. Finally, we describe potential therapeutic strategies in AD, based on the adiponectin paradox.

Angiotensin-(3-4) normalizes blood pressure, decreases Na+ and energy intake, but preserves urinary Na+ excretion in overweight hypertensive rats.

Hypertension, one of the most common and severe comorbidities of obesity and overweight, is a worldwide epidemic affecting over 30% of the population. We induced overweight in young male rats (aged 58 days) by exposure to a hypercaloric high lipid (HL) diet in which 70% of the calories originated from fat. The HL diet also contained 33 or 57% higher Na+ than the control (CTR) diet. Over the following weeks the HL rats gradually became overweight (490 ± 12 g vs 427 ± 7 g in the CTR group after 15 weeks) with high visceral fat. They developed elevated systolic blood pressure (SBP) (141 ± 1.9 mmHg), which was fully restored to CTR values (128 ± 1.1 mmHg) by oral administration of Ang-(3-4) (Val-Tyr), the shortest renin-angiotensin-derived peptide. The overweight rats had lower plasma Na+ concentration that augmented to CTR values by Ang-(3-4) treatment. Na+ ingestion was depressed by 40% as result of the Ang-(3-4) treatment, whereas the urinary excretion of Na+ (UNaV) remained unmodified. The preservation of UNaV after Ang-(3-4) treatment - despite the sharp decrease in the dietary Na+ intake - can be ascribed to the normalization of renal type 1 angiotensin II receptors and Na+-transporting ATPases, both up-regulated in overweight rats. These renal effects complete a counterregulatory action on elevated renin-angiotensin activity that allows the high SBP to be normalized and body Na+ homeostasis to be restored concomitantly in overweight rats.

Insights Into the Controversial Aspects of Adiponectin in Cardiometabolic Disorders.

In 2016, the World Health Organization estimated that more than 1.9 billion adults were overweight or obese. This impressive number shows that weight excess is pandemic. Overweight and obesity are closely associated with a high risk of comorbidities, such as insulin resistance and its most important outcomes, including metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Adiponectin has emerged as a salutary adipocytokine, with insulin-sensitizing, anti-inflammatory, and cardiovascular protective properties. However, under metabolically unfavorable conditions, visceral adipose tissue-derived inflammatory cytokines might reduce the transcription of the adiponectin gene and consequently its circulating levels. Low circulating levels of adiponectin are negatively associated with various conditions, such as insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease. In contrast, several recent clinical trials and meta-analyses have reported high circulating adiponectin levels positively associated with cardiovascular mortality and all-cause mortality. These results are biologically intriguing and counterintuitive, and came to be termed "the adiponectin paradox". Adiponectin paradox is frequently associated with adiponectin resistance, a concept related with the downregulation of adiponectin receptors in insulin-resistant states. We review this contradiction between the apparent role of adiponectin as a health promoter and the recent evidence from Mendelian randomization studies indicating that circulating adiponectin levels are an unexpected predictor of increased morbidity and mortality rates in several clinical conditions. We also critically review the therapeutic perspective of synthetic peptide adiponectin receptors agonist that has been postulated as a promising alternative for the treatment of metabolic syndrome and type 2 diabetes mellitus.

Effects of Blood Pressure Lowering Agents on Cardiovascular Outcomes in Weight Excess Patients: A Systematic Review and Meta-analysis.

BACKGROUND: Obesity hypertension is an ongoing pandemic. The first-line medications to treat this condition are still subject to debate. We compared diuretics, calcium-channel blockers (CCB), beta-blockers (BB), angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) as an initial antihypertensive therapy for prevention of cardiovascular morbimortality of hypertensive individuals who are overweight or obese. METHODS: We conducted a search of the literature for randomized clinical trials in which at least 50% of the participants were overweight or obese. The primary outcomes were all-cause mortality, cardiovascular mortality, acute myocardial infarction (MI), heart failure (HF), stroke, or end-stage renal disease. RESULTS: Our search yielded 16 randomized studies. Comparisons of two classes of drugs with at least two studies indicated that (1) CCB and ACEI increased the risk of HF [relative risk (RR) = 2.26; 95% confidence interval (CI) 1.16-4.40] and stroke [hazard ratio (HR) = 1.13; 1.00-1.26]), respectively, compared to diuretics; and (2) CCB showed a reduction in stroke (HR = 0.77; 0.66-0.89) and total mortality (HR = 0.94; 0.87-1.01) compared to the BB atenolol. Comparisons of two classes of antihypertensive medications with only one study showed that the risk of MI was higher with ARB valsartan versus CCB (HR = 1.19; 95% CI 1.02-1.38, p = 0.02). In contrast, losartan lowered the risk of a composite cardiovascular outcome compared to atenolol (HR = 0.87; 95% CI 0.77-0.98, p = 0.02). CONCLUSIONS: In hypertensive subjects with excess weight, diuretics are more effective for preventing HF and stroke than CCB and ACEI, respectively. CCB are a good first-line choice for prevention of cardiovascular disease, except HF.

High-molecular weight adiponectin/HOMA-IR ratio as a biomarker of metabolic syndrome in urban multiethnic Brazilian subjects.

Metabolic syndrome (MetS) has an important epidemiological relevance due to its increasing prevalence and association with type 2 diabetes and cardiovascular disease. Insulin resistance is a core feature of the MetS. HOMA-IR is a robust clinical and epidemiological marker of MetS. Adiponectin is an adipokine with insulin-sensitizing and anti-inflammatory functions; its levels decrease as number of components of MetS increases. High-molecular weight adiponectin (HMWA) is the multimer responsible for the relationship of adiponectin with insulin sensitivity. HOMA-IR and HMWA are suitable candidates for MetS biomarkers. The ratio of adiponectin to HOMA-IR has been validated as a powerful index of MetS and considered a better marker of its presence, than either HOMA-IR or adiponectin alone, in selected homogeneous populations. We compared the strength of association between HMWA, HOMA-IR and HMWA/HOMA-IR ratio with MetS and its key components. Our data have shown that the median (25th, 75th percentile) of HMWA/HOMA-IR ratio was lower in subjects with MetS [0.51 (0.33, 1.31)] as compared to those without it [2.19 (1.13, 4.71)]. The correlation coefficient (r) was significantly higher for HMWA/HOMA-IR ratio as compared to HMWA for waist circumference (-0.65; -0.40, respectively); mean blood pressure (-0.27; -0.14, respectively); fasting glucose (-0.38; -0.19, respectively); HDL-cholesterol (0.44; 0.40, respectively); and triglycerides (-0.35; -0.18, respectively). In a multivariable logistic regression analysis, the HMWA/HOMA-IR ratio was a sensitive predictor for MetS, being the only marker that was significantly associated with each and all the individual components of the syndrome. These results expand on previous studies in that we used the active circulating form of adiponectin, i.e. HMWA, and represent a typical Brazilian cohort characterized by intense interethnic admixture. Thus, the HMWA/HOMA-IR ratio is a minimally invasive biomarker for MetS that could be clinically useful in prognosing patient outcome.

Circulating Endocannabinoids and the Polymorphism 385C>A in Fatty Acid Amide Hydrolase (FAAH) Gene May Identify the Obesity Phenotype Related to Cardiometabolic Risk: A Study Conducted in a Brazilian Population of Complex Interethnic Admixture.

The dysregulation of the endocannabinoid system is associated with cardiometabolic complications of obesity. Allelic variants in coding genes for this system components may contribute to differences in the susceptibility to obesity and related health hazards. These data have mostly been shown in Caucasian populations and in severely obese individuals. We investigated a multiethnic Brazilian population to study the relationships among the polymorphism 385C>A in an endocannabinoid degrading enzyme gene (FAAH), endocannabinoid levels and markers of cardiometabolic risk. Fasting plasma levels of endocannabinoids and congeners (anandamide, 2-arachidonoylglycerol, N-oleoylethanolamide and N-palmitoylethanolamide) were measured by liquid chromatography-mass spectrometry in 200 apparently healthy individuals of both genders with body mass indices from 22.5 ± 1.8 to 35.9 ± 5.5 kg/m2 (mean ± 1 SD) and ages between 18 and 60 years. All were evaluated for anthropometric parameters, blood pressure, metabolic variables, homeostatic model assessment of insulin resistance (HOMA-IR), adiponectin, leptin, C-reactive protein, and genotyping. The endocannabinoid levels increased as a function of obesity and insulin resistance. The homozygous genotype AA was associated with higher levels of anandamide and lower levels of adiponectin versus wild homozygous CC and heterozygotes combined. The levels of anandamide were independent and positively associated with the genotype AA position 385 of FAAH, C-reactive protein levels and body mass index. Our findings provide evidence for an endocannabinoid-related phenotype that may be identified by the combination of circulating anandamide levels with genotyping of the FAAH 385C>A; this phenotype is not exclusive to mono-ethnoracial populations nor to individuals with severe obesity.

Association between leptin and its soluble receptor with cardiometabolic risk factors in a Brazilian population.

BACKGROUND: Most studies evaluating the conjoint effects of leptin and human soluble leptin receptor (hs-LR) on cardiometabolic risk factors have been conducted in well-characterized ethnic groups. We aimed to assess the associations of leptin and hs-LR with the cardiometabolic risk factors that reflect the components of metabolic syndrome (MetS) in a Brazilian population with varying degrees of adiposity. METHODS: This is a cross-sectional analysis of adult subjects (n=173, age 45 ± 12 years, 124 women; body mass index [BMI] 35.6 ± 9.5 kg/m(2)) for association of leptin and its soluble receptor with cardiometabolic risk factors (glucose, BMI, waist circumference, hip circumference, blood pressure, insulin, cholesterol and triglycerides). Plasma hs-LR was measured by ELISA; insulin and leptin were determined by RIA. Metabolic syndrome was defined by NCEP/ATP III. RESULTS: Leptin was positively associated with blood pressure, BMI, waist circumference, hip circumference, triglycerides, glucose, insulin and HOMA and inversely correlated with HDL-cholesterol. The hs-LR exhibited inverse relationship with cardiometabolic risk factors (P ≤ 0.006), except for glucose and lipid parameters. Leptin increased, whereas hs-LR decreased, with increasing number of MetS components (P for trend<0.001). In multivariable models, sex, BMI and insulin were independently associated with leptin, whereas age, sex, BMI and systolic blood pressure were the independent correlates of hs-LR. CONCLUSION: In a Brazilian population with complex interethnic admixture, levels of hs-LR and leptin were independently associated with systolic blood pressure and insulin, respectively. Leptin increased with increasing number of MetS components. In turn, hs-LR decreased as the number of MetS components increased.

Skin capillary density and microvascular reactivity in obese subjects with and without metabolic syndrome.

Obesity is associated with increased cardiovascular morbidity and mortality. We hypothesized that microvascular function may be impaired in obese subjects with metabolic syndrome (OB-MetSnd) compared to obese subjects without MetSnd (OB) and healthy subjects (HS). In this cross-sectional study, we evaluated skin capillary density (SCD) in OB-MetSnd (n=20, 12 women, BMI=36.5±1.1kg/m(2)), OB (n=25, 16 women, BMI=34.5±0.7kg/m(2)), and HS (n=30, 22 women, BMI=22.8±0.3kg/m(2)) groups. SCD was evaluated by intravital video-microscopy at rest and after post-occlusive reactive hyperemia (PORH) and venous congestion (VC). OB-MetSnd subjects exhibited significant differences in the values of MetSnd components and in leptin and HOMA-IR levels compared to OB and HS individuals. There were no differences in SCD among groups in resting conditions. The OB-MetSnd group failed to show a significant increase in the number of recruited capillaries during PORH and VC compared to the SCD evaluated at rest. A negative correlation of SCD with waist circumference, BMI, blood pressure, and HOMA-IR was observed after PORH and VC. When obese subjects were analyzed according to their HOMA-IR quartiles, a significant decrease in SCD was observed during POHR (P=0.02). Our findings showed that obese subjects have structural and functional alterations in skin microcirculation that are proportional to the increase in the degree of global and central obesity. In addition, in OB-MetSnd subjects, the cutaneous capillaries at rest are already maximally recruited, indicating an absence of functional capillary reserve. This may be related to the insulin resistance observed in OB-MetSnd individuals.

Hypoadiponectinemia is associated with prehypertension in obese individuals of multiethnic origin.

BACKGROUND: Considering that prehypertension is associated with an increase in cardiovascular risk, hypoadiponectinemia seems to be a predictor of hypertension. HYPOTHESIS: This study investigated whether adiponectin plasma levels are affected in Brazilian obese prehypertensives compared with those in normotensives and hypertensives. METHODS: The study involved 96 multiethnic obese subjects (mean age = 42.8-11.9 years; BMI = 35.7-7.3 kg/m(2)). Fasting plasma adiponectin and serum insulin were determined by radioimmunoassay. Insulin resistance was estimated by HOMA-IR. Blood pressure was recorded using a calibrated automated sphygmomanometer. RESULTS: Adiponectin concentrations were significantly lower in prehypertensives compared with those in normotensives, but hypertensives exhibited the lowest adiponectin concentrations of all. Regarding the values of HOMA-IR, both prehypertensives and hypertensives were significantly more insulin resistant when compared with normotensives. When normotensives and prehypertensives were classified according to the 50th percentile of adiponectin (< or = vs > 6.5 mg/ml) a logistic regression was performed to estimate the association of this adipokine with hypertension, the lower the plasma adiponectin values, the greater the association. A multivariate linear regression analysis adjusted for cardiometabolic factors showed that systolic blood pressure increased by 1.612 mm Hg for 1 microg/mL reduction in adiponectin plasma levels (P < 0.01). CONCLUSION: Our findings have shown that hypoadiponectinemia is associated with prehypertension in obese individuals of multiethnic origin.

Temporal relation between body mass index and renal function in individuals with hypertension and excess body weight.

OBJECTIVE: Recent evidence has suggested obesity as an independent risk factor for chronic kidney disease. However, the temporal relation between body mass index (BMI) and early renal dysfunction is unknown. This study aimed at evaluating whether longitudinal variations in BMI would reflect on changes in estimated glomerular filtration rate (GFR) in hypertensive individuals with excess body weight. METHODS: This was a cross-sectional, longitudinal study. RESULTS: Of the 218 participants who attended the first examination, 150 were available for paired final analyses. At the end of follow-up, GFR decreased by 1.024 mL/min for each 1-kg/m(2) increment in BMI (P<0.03). When BMI was analyzed in quartiles, a positive graded relation with GFR changes was observed in quartiles 1 and 2 (individuals who maintained or lost weight), and a negative relation in quartiles 3 and 4 (individuals who gained weight, P=0.05). A significant difference was observed between the smallest and highest BMI quartiles (P=0.01). At the end of follow-up, the 76 participants (51%) who gained weight (+4.6+/-0.4 kg) showed a reduction in GFR (-2.99+/-1.99 mL/min) of borderline significance (P=0.06) and a significant increase in fasting plasma glucose and triacylglycerol levels. Conversely, the 74 participants who maintained or lost weight showed no significant change in GFR and in fasting plasma glucose and triacylglycerol levels, although their blood pressure decreased significantly. CONCLUSIONS: Our study showed a significant temporal association between changes in BMI and GFR in overweight and obese hypertensive patients.

Not all obese subjects of multiethnic origin are at similar risk for developing hypertension and type 2 diabetes.

BACKGROUND: Whether insulin resistance and not obesity per se is the major contributor to clinical outcomes associated with obesity has not been fully established. This study evaluated in a group of obese Brazilians of multiethnic origin to what extent the prevalence of hypertension and other cardiometabolic risk factors varies as a function of the degree of insulin sensitivity. METHODS: The study involved 118 individuals (mean age of 44+/-12 years; BMI=38.6+/-7.9 kg/m(2)) without evidence of diabetes or cardiovascular disease. Insulin resistance was assessed by HOMA-IR index, which was used to stratify patients into tertiles. RESULTS: The mean HOMA-IR in tertile 1, the most insulin-sensitive group, was 2.7+/-0.8 and in tertile 3, the most insulin-resistant group, 9.1+/-2.4 (P<0.001). Mean arterial pressure showed a linear and significant variation across the HOMA-IR tertiles 1, 2, and 3 (94.3+/-11.7; 98.7+/-11.4; 105.0+/-12.4 mm Hg), as did fasting plasma glucose (93.6+/-12.1; 98.1+/-12.7; 100.0+/-11.0 mg/dL), uric acid (4.7+/-1.4; 5.9+/-1.9; 6.3+/-1.4 mg/dL), HDL-cholesterol (48.1+/-11.6; 46.5+/-10.5; 42.2+/-8.0 mg/dL), and plasma adiponectin (7.8+/-3.3; 7.0+/-2.8; 6.3+/-6.5 microg/mL), respectively. The results indicated that 27.5% of our patients had dysglicemia, 28.2% had hypertriglyceridemia, and 30.7% had arterial hypertension in the most insulin-sensitive tertile, when compared with 51%, 53.8% and 79.4%, respectively, in the most insulin-resistant tertile. A stepwise regression analysis showed that only HOMA-IR and age independently affected the risk for increased systolic blood pressure. CONCLUSION: In conclusion, our findings have shown that the risk of developing essential hypertension, type 2 diabetes, and cardiovascular disease is accentuated in obese individuals who are also more insulin resistant.

Association of a common variant of the leptin gene with blood pressure in an obese Brazilian population.

BACKGROUND: This study assessed in obese Brazilians subjects whether a common variant of leptin gene, -2548G>A, is associated with blood pressure changes. METHODS: A total of 140 subjects, 99 women; mean age of 45.2 +/- 12.4 years; body mass index (BMI) = 38.5 +/- 8.0 kg/m2 were included. Blood pressure was recorded using Dinamap 1846 (Critikon, Tampa, FL). Molecular analysis was made by use of PCR and restriction fragment-length polymorphism analysis. Plasma insulin and leptin concentrations were determined by radioimmunoassay. RESULTS: AA homozygotes, in comparison with the G-allele carriers, showed significant lower levels of systolic, diastolic, and mean arterial pressure (120 +/- 10 vs. 132 +/- 17 mm Hg, P = 0.01; 75 +/- 6 vs. 84 +/- 12 mm Hg, P = 0.009; 92 +/- 7 vs. 100 +/- 12 mm Hg, P = 0.007, respectively). The differences in blood pressure remained significant after adjusting for the influence of gender, age, obesity, and body fat distribution as well as for leptin, insulin, and homeostasis model assessment of insulin resistance. A stepwise regression analysis confirmed that the LEP AA genotype independently predicted blood pressure changes. On the other hand, in GG homozygotes, insulinemia showed a significant association with blood pressure values. This suggests that common LEP genotype carriers exhibiting high insulin levels, reflecting an insulin-resistant state, were particularly prone to higher blood pressure levels. CONCLUSIONS: Our results showing that higher blood pressure levels were found with the most prevalent -2548G>A genotype, whereas patients with the AA genotype seemed to be protected from hypertension, indicate that the -2548G>A polymorphism of LEP appears to be an important mediator of obesity hypertension.

Treatment of hypertension in individuals with the cardiometabolic syndrome: role of an angiotensin II receptor blocker, telmisartan.

Arterial hypertension is a global public health problem owing to its high prevalence and association with increased risk for cerebral, cardiac and renal events. Hypertension frequently clusters with other cardiometabolic risk factors, such as dysglycemia, low levels of high-density lipoprotein cholesterol and high triglyceride levels. These, along with other factors such as central obesity, increased inflammation, endothelial dysfunction and thrombosis, are components of the metabolic syndrome. All guidelines recommend that the first-line therapy in metabolic syndrome should be based on lifestyle modification, consisting of diet and moderate exercise for at least 30 min/day. Concerning drug treatment of hypertension associated with other cardiometabolic risk factors, many results of head-to-head studies have demonstrated a reduction in new-onset Type 2 diabetes in hypertensive patients treated with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, when compared with conventional antihypertensive therapy. The explanations of the different actions of both these drugs include several mechanisms related to pancreatic insulin release and insulin sensitivity improvement. Another mechanism by which the inhibition of the renin-angiotensin system may improve insulin sensitivity is through the partial peroxisome proliferator-activated receptor-gamma agonism of telmisartan. For that reason, telmisartan has been considered by some experts to be an antihypertensive agent that is particularly useful in the treatment of hypertension associated with cardiometabolic risk factors. The impact of the promising metabolic action exhibited by telmisartan on the outcome of hypertensive patients aggregating other cardiometabolic risk factors waits for adequately randomized and powered clinical trials.

Hypoadiponectinemia is associated with blood pressure increase in obese insulin-resistant individuals.

Adiponectin is a major adipocytokine and has been considered as an independent risk factor for arterial hypertension. Most studies on the subject have been restricted to biracial (white-black) and Asian groups. The present report examined whether adiponectin affects blood pressure in a sample of untreated obese Brazilians of multiethnic origin. Fasting plasma adiponectin and serum insulin were determined by radioimmunoassay. Insulin resistance was estimated by homeostatic model assessment of insulin resistance (HOMA-IR). Blood pressure was recorded using Dinamap 1846 (Critikon, Tampa, FL). Adiponectin was significantly lower in obese hypertensive individuals than in obese normotensive ones. Blood pressure, insulin, and HOMA-IR were significantly higher in obese hypertensive than in obese normotensive individuals. Plasma adiponectin was negatively associated with waist-to-hip ratio, blood pressure, insulin, and HOMA-IR. The comparison of obese individuals who markedly differed in their HOMA-IR (> vs 6. 5 microg/mL), a 3 x 2 analysis of variance showed an independent contribution of adiponectin in the variation of mean arterial pressure. These results support the notion that HOMA-IR and adiponectin independently predict blood pressure variation in obese insulin-resistant Brazilians.

[Effects of greater-than-5% weight reduction on hemodynamic, metabolic and neuroendocrine profiles of grade I obese subjects]. / Efeitos da redução de peso superior a 5% nos perfis hemodinâmico, metabólico e neuroendócrino de obesos grau I.

OBJECTIVE: To evaluate the effects of a greater-than-5% weight reduction in hemodynamic, metabolic, and neuroendocrine profiles of grade I obese subjects. METHODS: Observational study with 47 grade I obese subjects, with mean age of 33 years who received monthly orientation regarding diet, physical exercises, and eating behavior for four months. Blood pressure using the auscultatory method and pulse rate were assessed monthly, whereas the following variables (and respective methods) were measured at the beginning and at the end of the study: total cholesterol, triglycerides, HDL-cholesterol (enzymatic method), LDL-cholesterol (Friedewald formula), blood glucose (hexokinase method), leptin, adiponectin, renin, aldosterone, insulin (radioimmunoassay) and insulin-resistance index (HOMA). RESULTS: After adjustment for other variables, significant reductions of 6 mmHg in diastolic blood pressure, 7 pg/ml in renin, 13 mg/dl in total cholesterol and 12 mg/dl in LDL-cholesterol were observed in the greater-than-5% weight reduction group. Also, a tendency to a higher increase in adiponectin levels by the end of the study, as well as a three-fold higher reduction in blood glucose, insulin, and HOMA levels, and a six-fold higher reduction in leptin levels were observed in this group. CONCLUSION: Non-pharmacological measures that promote a greater-than-5% weight reduction produce hemodynamic, metabolic, and neuroendocrine effects that improve the cardiovascular risk of obese subjects.

Efeitos da redução de peso superior a 5 por cento nos perfis hemodinâmico, metabólico e neuroendócrino de obesos grau I / Effects of greater-than-5 percent weight reduction on hemodynamic, metabolic and neuroendocrine profiles of grade I obese subjects

OBJETIVO: Avaliar os efeitos da redução de peso superior a 5 por cento nos perfis hemodinâmico, metabólico e neuroendócrino de obesos grau I. MÉTODOS: Estudo observacional com 47 obesos grau I, média de idade de 33 anos, submetidos a orientação mensal quanto a dieta, exercício físico e comportamento alimentar, durante quatro meses. A pressão arterial, pelo método auscultatório, e a freqüência cardíaca, pelo método palpatório, foram avaliadas mensalmente, enquanto as seguintes variáveis (e respectivos métodos) foram medidas no início e final do estudo: colesterol total, triglicerídeos, HDL-colesterol (enzimático), LDL-colesterol (fórmula de Friedwald), glicemia (enzimático hexoquinase), leptina, adiponectina, renina, aldosterona, insulina (radioimunoensaio) e índice de resistência à insulina (HOMA). RESULTADOS: Observamos, após ajuste para outras variáveis, reduções significativas de 6 mmHg na pressão arterial diastólica, 7 pg/ml na renina, 13 mg/dl no colesterol total e 12 mg/dl no LDL-colesterol, no grupo com redução de peso superior a 5 por cento. Notamos, também nesse grupo, tendência ao aumento de maior magnitude da adiponectina ao final do estudo, bem como diminuição três vezes maior dos níveis de glicemia, insulina e HOMA, e seis vezes maior da leptina. CONCLUSÃO: Medidas não-farmacológicas capazes de promover redução de peso superior a 5 por cento produzem efeitos hemodinâmicos, metabólicos e neuroendócrinos que melhoram o risco cardiovascular de obesos.