Insulin and leptin: disputable and unsolved questions of their interaction in Obesity

Leptin and its receptor are widely distributed mainly in white adipose tissue. Serum leptin concentration correlates with body mass index, and its levels decrease with fasting. Insulin appears to increase leptin messenger RNA, protein expression and release by adipocytes, both synthesized both in advance and de novo, and reduces the levels of adiponectin and its receptors. According to the literature, chronic hyperinsulinemia increases leptin levels. This review summarizes the latest knowledge on the effect of insulin on leptin synthesis and secretion; cellular mechanisms that control the synthesis and release of white adipose tissue are presented.Лептин и его рецептор широко распространены главным образом в белой жировой ткани. концентрация лептина в сыворотке крови коррелирует с индексом массы тела, а его уровни снижаются при голодании. Инсулин, по-видимому, увеличивает матричную РНК лептина, экспрессию белка и его высвобождение адипоцитами, причем синтезированного как предварительно, так и de novo, и снижает уровни адипонектина и его рецепторов. Согласно литературным данным, хроническая гиперинсулинемия повышает уровень лептина. В этом обзоре обобщены последние знания о влиянии инсулина на синтез и секрецию лептина; представлены клеточные механизмы, контролирующие синтез и высвобождение белой жировой тканью

CYTOKINE PROFILE IN VISCERAL OBESITY AND ADVERSE CARDIOVASCULAR PROGNOSIS OF MYOCARDIAL INFARCTION

Presence of myocardial infarction in patients with obesity can lead to an uncontrolled increase in proinflammatory cytokines and unfavorable course of the pathological process. Objective: to study the relationship of key inflammatory factors and the development of complications at different terms after myocardial infarction in patients with visceral obesity. The study involved 94 men with myocardial infarction. Visceral obesity was diagnosed by multi-slice computed tomography (LightspeedVCT 64 ,General Electric,USA). On the 1st and 12th day of hospitalization, we determined serum concentrations of interleukins (TNFα, IL-1β, IL-6, IL-8 IL-10 and IL-12), and C-reactive protein. Adverse cardiovascular events were documented during the next year. The most informative indicators were identified by a stepwise logistic regression analysis. In patients with myocardial infarction an imbalance of cytokine profile revealed, i.e., an increase in proinflammatory markers (TNFα, IL-1β, IL-6, IL-8, IL-12, CRP), along with decrease in IL-10, being more pronounced in cases of visceral obesity. Among the studied markers, closest relationship was observed between visceral obesity and serum concentrations of IL-6 and CRP. Over the year, adverse cardiovascular events proved to be more frequent in patients with visceral obesity. Post-infarction complication risk was associated with higher concentrations of IL-6, IL-12 and IL-10 deficiency. Hence, development of adverse cardiovascular events within a year after myocardial infarction is more typical to the patients with visceral obesity, and is accompanied by activation of proinflammatory cytokines and IL-10 deficiency

INSULIN AND LEPTIN: DISPUTABLE AND UNSOLVED QUESTIONS OF THEIR INTERACTION

Leptin and its receptor are widely distributed mainly in white adipose tissue. Serum leptin concentration correlates with body mass index, and its levels decrease with fasting. Insulin appears to increase leptin mRNA and protein expression, as well as release by adipocytes, synthesized both in advance and de novo, and reduces the levels of adiponectin and its receptors. According to the literature, chronic hyperinsulinemia increases leptin levels. This review summarizes the latest knowledge on the effect of insulin on leptin synthesis and secretion; cellular mechanisms that control the synthesis and release of white adipose tissue are presented

CLINICAL AND BIOCHEMICAL PREDICTORS OF DIABETES MELLITUS MANIFESTATION AFTER MYOCARDIAL INFARCTION

Aim. To identify the most informative parameters of carbohydrate and lipid metabolism which predict the manifestation of type 2 diabetes mellitus (DM-2) within one year after myocardial infarction (MI).Material and methods. The study included 200 MI patients who underwent the assessment of glucose and insulin levels, insulin resistance (IR) index, and lipid profile at Days 1 and 12. The incidence of new DM-2 cases which manifested within a year after MI was assessed.Results. After one year after MI, incident DM-2 was diagnosed in 14,5% of the patients. It was associated with concomitant cardiovascular risk factors, adverse clinical course of acute and longer-term MI periods, and lipid metabolism disturbances. A higher risk of incident DM-2 after MI was linked to IR and an elevation in free fatty acid (FFA) levels (9,5 times or higher) during the acute MI phase.Research Institute for Complex Cardiovascular Disease Issues, Siberian Branch, Russian Academy of Medical Sciences, Kemerovo; 2Kemerovo State Medical Academy, Kemerovo; 3Siberian State Medical University, Tomsk, Russia

Associations of adipocytokine expression and cardiovascular risk factors in stable coronary artery disease

Aim. To determine the expression of adiponectin, leptin and I interleukin-6 (IL-6) in subcutaneous, epicardial and perivascular adipose tissue, depending on the presence of cardiovascular risk factors.Material and methods. The study included 90 patients with stable coronary artery disease (CAD) who underwent coronary artery bypass grafting. Samples of adipose tissue were obtained during surgery. The levels of matrix ribonucleic acid (mRNA) of the studied adipocytokines were determined in the presence/absence of the main cardiovascular risk factors.Results. Differences in the expression of genes of the studied adipocytokines in different sex and age groups of patients were revealed, depending on the tissue belonging of adipocytes. Expression of adiponectin in the epicardial and perivascular adipose tissue (EАT and PVAT, respectively), as well as of leptin in the PVAT was less pronounced in men. However, the level of IL-6 mRNA in the subcutaneous adipose tissue (SAT) of men was three times higher than in women, and in the PVAT it was lower. The maximum expression of leptin and IL-6 in the EAT and PVAT was found in persons aged 50-59 years. The presence of dyslipidemia is associated with a decrease in the expression of adiponectin in the EAT, PVAT, and IL-6 in the PVAT. In patients with hypertension (HTN), there was a low level of adiponectin mRNA in the EAT against the background of high leptin levels in the EAT and IL-6 in SAT and EAT. In hypertension with a duration of more than 20 years, there was a decrease in adiponectin expression and an increase in leptin in all types of AT. In smokers, an increase in the expression of adiponectin in the SAT, EAT, PVAT and leptin in the SAT, EAT was found.Conclusion. Associations of traditional cardiovascular risk factors with imbalance of adipocytokines of local fat depots in patients with CAD were revealed. The detected imbalance is manifested by a decrease in the expression of cardioprotective adiponectin in the EAT, PVAT, an increase in leptin and IL-6, which is an unfavorable sign. The presence of such risk factors as male sex, age of 50-59 years, dyslipidemia and hypertension in patients can enhance atherogenesis and contribute to the further progression of CAD

INSULIN RESISTANCE MARKERS IN PATIENTS WITH ST SEGMENT ELEVATION MYOCARDIAL INFARCTION

In general population and among diabetic patients, insulin resistance (IR) is regarded as a cardiovascular risk factor. The aim of this study was to assess the dynamics of IR markers among non-diabetic and diabetic (Type 2 diabetes mellitus, DM-2) patients with acute myocardial infarction and ST segment elevation (STEMI) in the acute and early reconvalescent phases. In non-diabetic patients, clinical course of STEMI was characterised by IR development, postprandial hyperglycemia and hyperinsulinemia, as well as elevated levels of free fatty acids (FFA) and plasminogen activator inhibitor (PAI). Persistent high levels of FFA and PAI during stabilization phase in STEMI patients could justify the use of IR markers as one of the criteria for DM-2 risk and for the start of secondary prevention of metabolic MI complications

Dose-dependent effects of atorvastatin in the hospitalisation period of myocardial infarction

Aim. To compare the dynamic effects of atorvastatin doses 20 mg and 40 mg on lipid profile, insulin resistance markers, adipokines, prothrombotic, and proinflammatory status in myocardial infarction (MI) patients during the hospitalisation period. Material and methods. The study included 42 patients with ST segment elevation MI. Group 1 (n=21) received atorvastatin in the dose of 40 mg/day; Group 2 (n=21) was administered atorvastatin in the dose of 20 mg/day. At Day 1 and Day 12 after admission, the parameters of lipid profile (total cholesterol and its fractions, atherogenic index, free fatty acids, and triglycerides), carbohydrate metabolism (glucose, insulin, and C-peptide), insulin resistance (HOMA index), proinflammatory status (C-reactive protein and interleukin-6), prothrombotic status (plasminogen activator inhibitor-1), and adipokines (leptin, resistin, and adiponectin) were measured. Results. Dose-dependent effects of atorvastatin were already demonstrated in the early hospitalisation period: the 40 mg dose was more effective in terms of lipid profile improvement, while the 20 mg dose was more effective for insulin resistance correction. The increase in atorvastatin dose up to 40 mg was associated with a reduction in pancreatic insulin-producing function. The effects on inflammation and thrombogenesis markers were less dose-dependent. A lower dose of atorvastatin (20 mg) normalized adipokine levels (increased leptin concentration and increased protective effects of resistin), which could be regarded as a beneficial prognostic factor. Conclusion. The selection of atorvastatin dose in MI patients should take into account the adipokine status and the dynamics of biochemical markers of insulin resistance

Expression of adipocytokines in heart fat depots depending on the degree of coronary artery atherosclerosis in patients with coronary artery disease.

In coronary artery disease (CAD) the adipocytokine content in the heart fat depot is altered, but it has not been established whether these changes are associated with the degree of atherosclerotic damage to the coronary artery (CA). Were examined 84 patients with CAD, and according to the degree of atherosclerotic state based on the SYNTAX Score scale, were divided: 39 moderate (≤22 points), 20 severe (23-31 points) and 25 extremely severe (≥32 points). Biopsies of subcutaneous (SAT), epicardial (EAT) and perivascular adipose tissue (PVAT) were obtained during elective coronary artery bypass grafting (CABG). The expression of adipocytokine was determined using real-time PCR. The concentration of the studied adipocytokines in adipocyte culture medium was measured by ELISA. Statistical analysis was performed using logistic regression analysis. In the adipocytes of the cardiac depot of patients with CAD, an increase in the expression and secretion of leptin and IL-6 and a decrease in adiponectin, with a maximum manifestation in severe and extremely severe CA lesions, was observed. EAT adipocytes were characterized by minimal expression of the adiponectin gene maximal gene expression leptin and IL-6 compared to SAT and PVAT adipocytes