In the Pursuit of Metabolic Markers of Systemic Sclerosis-Plasma Adiponectin and Omentin-1 in Monitoring the Course of the Disease.

Systemic sclerosis (SSc) is a connective tissue disease leading to cutaneous and visceral fibrosis. Pathological features of SSc include immune dysregulation, vasculopathy, and impaired angiogenesis. Adipokines act as cytokines and hormones and are involved in various pathological processes, including metabolic disorders, inflammation, vasculopathy, and fibrosis. This study aimed to determine the level of omentin-1 and adiponectin to evaluate their potential role in the pathogenesis of SSc. We assessed serum omentin-1 and adiponectin as well as metabolic parameters in 58 patients with SSc and 30 healthy controls. The follow-up was performed in SSc individuals. Omentin-1 levels were significantly higher in SSc individuals as compared to the controls. In post-hoc analysis, omentin-1 was higher in the group with disease duration ≥7 years than in the control group. A positive correlation was noted between disease duration and both adipokines and increased with longer disease duration. However, there were no correlations between selected adipokines and metabolic parameters. Enhanced omentin-1 levels and higher levels of omentin-1 in patients with longer disease duration may suggest that omentin-1 is involved in the pathomechanisms of SSc as its concentrations are not directly related to BMI, age, and insulin resistance.

Inflammasome NLRP3 Potentially Links Obesity-Associated Low-Grade Systemic Inflammation and Insulin Resistance with Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of neurodegenerative dementia. Metabolic disorders including obesity and type 2 diabetes mellitus (T2DM) may stimulate amyloid ß (Aß) aggregate formation. AD, obesity, and T2DM share similar features such as chronic inflammation, increased oxidative stress, insulin resistance, and impaired energy metabolism. Adiposity is associated with the pro-inflammatory phenotype. Adiposity-related inflammatory factors lead to the formation of inflammasome complexes, which are responsible for the activation, maturation, and release of the pro-inflammatory cytokines including interleukin-1ß (IL-1ß) and interleukin-18 (IL-18). Activation of the inflammasome complex, particularly NLRP3, has a crucial role in obesity-induced inflammation, insulin resistance, and T2DM. The abnormal activation of the NLRP3 signaling pathway influences neuroinflammatory processes. NLRP3/IL-1ß signaling could underlie the association between adiposity and cognitive impairment in humans. The review includes a broadened approach to the role of obesity-related diseases (obesity, low-grade chronic inflammation, type 2 diabetes, insulin resistance, and enhanced NLRP3 activity) in AD. Moreover, we also discuss the mechanisms by which the NLRP3 activation potentially links inflammation, peripheral and central insulin resistance, and metabolic changes with AD.

The role of leptin in selected skin diseases.

Leptin is an adipokine, adipocyte-derived compound, which acts both as a hormone and cytokine. It is mainly synthesized by adipocytes of white adipose tissue. Leptin possesses pleiotropic functions including, among others, stimulation of angiogenesis and production of proinflammatory cytokines. The various types of leptin activity are related to the wide distribution of leptin receptors. This adipokine acts by activating intracellular signaling cascades such as JAKs (Janus kinases), STATs (signal transducers and activators of transcription), and others.In a course of obesity, an increased serum level of leptin coexists with tissue receptor resistance. It has been reported that enhanced leptin levels, leptin receptor impairment, and dysfunction of leptin signaling can influence skin and hair. The previous studies revealed the role of leptin in wound healing, hair cycle, and pathogenesis of skin diseases like psoriasis, lupus erythematosus, and skin cancers. However, the exact mechanism of leptin's impact on the skin is still under investigation. Herein, we present the current knowledge concerning the role of leptin in psoriasis and selected skin diseases.

Insulin and brain aging.

The world's population is living much longer than in the past. It is crucial to find as many pathological factors that deteriorate the health condition and well-being of elderly people as possible. Loss of activity and functions over time is typical for elderly people. Aging affects brain function, metabolism and structure in different ways, and these effects have multiple etiologies. Cognitive impairment, impaired neurotransmitter activity and reduction of brain volume are observed in the elderly population. The process of brain aging is associated with a decrease of central insulin concentration as well as impairment of insulin receptor binding ability, resulting in deterioration of glucose homeostasis in the brain. Peripheral insulin resistance is a typical feature of older age. Data from the literature suggest that high circulating insulin and insulin resistance are important contributors to progressive cognitive impairment and neurodegenerative processes. The maintenance of insulin sensitivity and proper insulin signaling may lead to preserved cognition that results in well-being of elderly people.

Nicotinic acid attenuates amyloid ß1-42-induced mitochondrial dysfunction and inhibits the mitochondrial pathway of apoptosis in differentiated SH-SY5Y cells.

Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by progressive memory loss and behavioral disorders. The excessive accumulation of amyloid ß (Aß) and the formation of neurofibrillary tangles (NFTs) damage synaptic connections and the death of neurons. However, the underlying mechanisms of pathogenesis of AD remain unclear. Growing evidence indicates that impaired mitochondrial function may play a crucial role in the development of AD. In the current study, we investigated whether nicotinic acid (NA) could protect against amyloid ß1-42-induced cytotoxicity in differentiated SH-SY5Y cells. Our results revealed the neuroprotective effects of NA on the differentiated SH-SY5Y cells treated with Aß1-42. In detail, the 1-h pre-incubation with NA increased cell viability and lowered LDH levels. NA pre-incubation abolished Aß1-42 treatment-associated alterations of mRNA levels of synaptic genes and enhanced the relative ß3 Tubulin fluorescence intensity. NA eliminated the Aß1-42-induced mitochondrial dysfunction by increasing the potential of mitochondrial membranes and maintaining a balance between the fusion and fission of mitochondria. Moreover, Aß1-42 decreased mRNA levels of anti-apoptotic bcl2 and increased mRNA levels of pro-apoptotic: bim, bak, cytochrome c, and caspase 9. At the same time, the NA pre-treatment reduced Aß1-42-dependent apoptotic death of differentiated SH-SY5Y cells. The above data suggest that NA presents a protective activity against Aß1-42-induced cytotoxicity in differentiated SH-SY5Y cells by inhibiting the mitochondrial pathway of apoptosis and restoring the proper function of mitochondria.

Resistin levels in women with ischemic stroke.

OBJECTIVES: Resistin may be an independent inflammatory marker of atherosclerosis. Therefore, its circulating level might be important prognostic factor of cardiovascular disease in humans. We aimed in this study to assess plasma resistin concentration in Polish women with acute ischemic stroke, who additionally suffer from chronic diseases: diabetes, hypertension and/or obesity. The changes of resistin levels after 10 days from the onset of stroke and possible associations between resistin and pro-inflammatory cytokine TNFα were also evaluated. MATERIAL AND METHODS: Material consisted of 41 women with ischemic stroke (aged 60-85 years) and 64 controls (aged 60-85 years). Circulating resistin and TNFα concentrations were measured using ELISA. Blood was taken twice in the stroke group, in the first and tenth day from the onset of clinical symptoms, and only once in the controls. Clinical and biochemical data (blood pressure, weight, height, glucose, insulin, lipid profile) were collected. RESULTS: Higher concentrations of resistin and TNFα were observed in ischemic stroke patients at the first day comparing to the controls. Second evaluation after 10 days in comparison with the first measurement revealed significantly higher TNFα levels and non-significant lower values of resistin. Resistin positively correlated with TNFα and stroke severity. CONCLUSIONS: Changes in resistin and TNFα concentrations were observed in the course of stroke. Further investigations are required to assess the implication of these findings. Higher resistin concentration might be associated with worse neurological deficits.

Therapy of obesity in women with PCOS using GLP-1 analogues - benefits and limitations [Terapia otylosci u kobiet z PCOS przy zastosowaniu analogów GLP-1 - korzysci i ograniczenia].

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder among women of reproductive age. The incidence ranges from approx. 6% to 20%. PCOS is characterized by a spectrum of symptoms and clinical features that includes ovarian dysfunction, clinical and/or biochemical hyperandrogenism, and ultrasound evidence of morphologically polycystic ovaries. Obesity is present in 40-70% of patients with the syndrome. Adiposity is involved in exacerbating the negative effects of insulin resistance, hyperinsulinaemia, and hyperandrogenaemia in the course of PCOS. Therefore, it is essential to maintain normal weight or effectively treat overweight/obesity in patients suffering from this endocrinopathy. Apart from diet and lifestyle interventions, an appropriate pharmacological or surgical treatment should be selected for the individual patient. Evidence-based data have unequivocally proven the validity of the use of glucagon-like peptide 1 (GLP-1) analogues in the treatment of overweight/obese patients with PCOS. The result of the GLP-1 therapy is not only a reduction of body weight but also an improvement in insulin resistance and a decrease in hyperandrogenaemia. It also seems that this treatment method increases spontaneous and in-vitro pregnancy rates. Therefore, the GLP-1 treatment of obese PCOS women is a new therapeutic opportunity not only for weight loss but also for a wide range of benefits. This review summarizes and discusses findings regarding obesity and its relation to hyperandrogenism and insulin resistance in PCOS, with special attention paid to the pharmacological treatment of adiposity with GLP-1 analogues.

The influence of cocaine-amphetamine regulated transcript (CART) on pituitary hormones, corticosterone and leptin levels in starved rats.

OBJECTIVE: CART is involved in the control of food intake and hormonal secretion. We aimed to evaluate the effects of CART on hormonal profile in starved rats. METHODS: Study group included 100 male rats. Under conditions of food limitation CART (55-102) was given centrally (icv) or peripherally (iv). Non-starved animals underwent identical procedure. Vehicle (aCSF or saline)-injected rats served and as a controls. 60 minutes after CART or vehicle administration blood was collected to assess pituitary hormones (LH, FSH, PRL, GH, ACTH, TSH), corticosterone and leptin concentrations. RESULTS: Itracerebroventricular CART injection resulted in a significant increase in PRL, GH and corticosterone concentrations in non-starved rats compared with vehicle injected animals. However, in a group of starved animals only leptin levels were decreased in comparison with fasted controls. Peripheral CART administration caused a significant increase in PRL, GH and TSH levels in non-starved rats but no changes in investigated hormone levels were observed in starved animals when compared to saline injected controls. CONCLUSIONS: Our results indicate that CART is able to modulate hormonal profile in a non-starved rats. However, the modulatory effect depends on the CART administration method. Interestingly, CART administration, both icv and iv, does not have an impact on pituitary hormones and corticosterone levels in a course of food limitation.

Decreased total serum adiponectin and its isoforms in women with acute ischemic stroke.

OBJECTIVE: An association between cerebral infarct risk factors and serum adiponectin levels (both total and separate isoforms) has previously been identified. The aim of this study was to assess circulating levels of all forms of adiponectin in the course of an ischemic stroke. MATERIAL AND METHODS: Adiponectin and its isoforms (HMW, MMW and LMW) were measured in serum samples taken from 38 women in the first 24 hours of cerebral infarct and 38 controls matched for gender, body mass index (BMI) and age. In addition, biochemical parameters (glucose, insulin, lipid profile) and clinical data (blood pressure, weight, and height) were evaluated. RESULTS: A significant reduction in serum levels of adiponectin and all examined fractions of this adipokine was observed in women suffering from acute ischemic stroke, compared with the matched controls. CONCLUSIONS: Differences in the serum adiponectin array between stroke subjects and controls were identified and further studies are required to investigate the clinical implications of this finding.

Contribution of Mitochondrial Dysfunction Combined with NLRP3 Inflammasome Activation in Selected Neurodegenerative Diseases.

Alzheimer's disease and Parkinson's disease are the most common forms of neurodegenerative illnesses. It has been widely accepted that neuroinflammation is the key pathogenic mechanism in neurodegeneration. Both mitochondrial dysfunction and enhanced NLRP3 (nucleotide-binding oligomerization domain (NOD)-like receptor protein 3) inflammasome complex activity have a crucial role in inducing and sustaining neuroinflammation. In addition, mitochondrial-related inflammatory factors could drive the formation of inflammasome complexes, which are responsible for the activation, maturation, and release of pro-inflammatory cytokines, including interleukin-1ß (IL-1ß) and interleukin-18 (IL-18). The present review includes a broadened approach to the role of mitochondrial dysfunction resulting in abnormal NLRP3 activation in selected neurodegenerative diseases. Moreover, we also discuss the potential mitochondria-focused treatments that could influence the NLRP3 complex.

The Beneficial Role of Natural Endocrine Disruptors: Phytoestrogens in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia with a growing incidence rate primarily among the elderly. It is a neurodegenerative, progressive disorder leading to significant cognitive loss. Despite numerous pieces of research, no cure for halting the disease has been discovered yet. Phytoestrogens are nonestradiol compounds classified as one of the endocrine-disrupting chemicals (EDCs), meaning that they can potentially disrupt hormonal balance and result in developmental and reproductive abnormalities. Importantly, phytoestrogens are structurally, chemically, and functionally akin to estrogens, which undoubtedly has the potential to be detrimental to the organism. What is intriguing, although classified as EDCs, phytoestrogens seem to have a beneficial influence on Alzheimer's disease symptoms and neuropathologies. They have been observed to act as antioxidants, improve visual-spatial memory, lower amyloid-beta production, and increase the growth, survival, and plasticity of brain cells. This review article is aimed at contributing to the collective understanding of the role of phytoestrogens in the prevention and treatment of Alzheimer's disease. Importantly, it underlines the fact that despite being EDCs, phytoestrogens and their use can be beneficial in the prevention of Alzheimer's disease.

Adipokines and genetic factors in overweight or obese but metabolically healthy Polish women.

OBJECTIVE: Obesity may be accompanied by enhanced metabolic disturbances but not all obese patients suffer from metabolic syndrome. Since metabolic homeostasis is under control of genetic factors underlying expression of adipokines, we aimed to compare the serum concentrations of adiponectin and resistin, and polymorphism in their genes, in overweight or obese Polish women. MATERIAL AND METHODS: The study included 265 women with BMI above 25 kg/m2 (140 metabolically healthy and 125 with metabolic syndrome) and 104 non-obese women as a control group. Anthropometric parameters (BMI, BIA, WHR), blood pressure, lipid, glucose and HOMA-IR profiles as well as serum concentrations of adiponectin, HMW adiponectin and resistin were evaluated. Gene polymorphisms of adiponectin gene (276G/T; 11377C/G; 11391G/A) and resistin gene (420C/G; 62G/A; 537A/C) were analyzed using TaqMan SNP genotyping assays. RESULTS: Higher serum concentrations of total adiponectin and lower levels of resistin were found in metabolically healthy patients when compared to those diagnosed with metabolic syndrome. No differences of serum HMW and resistin concentrations were observed between overweight or obese but metabolically healthy subjects and normal weight controls. No associations of investigated polymorphisms and the presence of metabolic syndrome were noticed in overweight/obese women with metabolic syndrome. CONCLUSIONS: The assessment of total adiponectin in sera seems to be promising target in distinguishing subjects with obesity who undergo a diagnostic procedure for metabolic syndrome. Moreover, the evaluation of adipokine array may help to select patients with higher risk of metabolic disturbances that are associated with severe diseases.

The Association of Obesity with Autoimmune Thyroiditis and Thyroid Function-Possible Mechanisms of Bilateral Interaction.

A growing number of patients suffer from autoimmune diseases, including autoimmune thyroid disease. There has simultaneously been a significant increase in the prevalence of obesity worldwide. It is still an open question whether adiposity can directly influence activation of inflammatory processes affecting the thyroid in genetically predisposed individuals. Adipokines, biologically active substances derived from the adipocytes, belong to a heterogenic group of compounds involved in numerous physiological functions, including the maintenance of metabolism, hormonal balance, and immune response. Notably, the presence of obesity worsens the course of selected autoimmune diseases and impairs response to treatment. Moreover, the excess of body fat may result in the progression of autoimmune diseases. Nutritional status, body weight, and energy expenditure may influence thyroid hormone secretion. Interestingly, thyroid hormones might influence the activity of adipose tissue as metabolic alterations related to fat tissue are observed under pathological conditions in which there are deficits or overproduction of thyroid hormones. Functioning TSH receptors are expressed on adipocytes. Thermogenesis may presumably be stimulated by TSH binding to its receptor on brown adipocytes. There could be a bilateral interaction between the thyroid and adipose. Obesity may influence the onset and course of autoimmune disease.

Peripheral levels of selected adipokines in patients with newly diagnosed multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. The exact aetiology is unknown. However, genetic and environmental factors are suggested to be involved in the pathogenesis of MS. Improper diet, resulting in obesity and metabolic syndrome, can contribute to this disease. Adipokines, secreted by adipose tissue, link the metabolism and immune system. MATERIAL AND METHODS: We aimed to assess plasma levels of selected adipokines in newly diagnosed, treatment-naïve individuals with multiple sclerosis. Our group comprised 58 individuals (31 MS patients and 27 controls, matched for age and BMI) without diabetes, hypertension, or dyslipidaemia. Circulating adiponectin and all adiponectin fractions, visfatin, and omentin concentrations were measured. Metabolic parameters were also assessed. RESULTS: In MS individuals we observed the following results: higher concentrations of visfatin, lower levels of omentin, and no differences in adiponectin array. There were also correlations between some adipokines and metabolic parameters. After adjustment to BMI, a significant decrease in total adiponectin, high-molecular weight (HMW) adiponectin and omentin, and an increase in medium-molecular-weight (MMW) adiponectin were observed in the group of MS patients when compared to those of the controls. CONCLUSIONS: Our results indicate that adiponectin with its fractions, visfatin, and omentin cannot be considered as causative factors in the early phase of multiple sclerosis. However, the potential role of adipokines in MS is possible because they might be involved in the pathogenesis of MS, regarded as an autoimmune disorder.

Vascular Dysfunction and Insulin Resistance in Aging.

Insulin was discovered in 1922 by Banting and Best. Since that time, extensive research on the mechanisms of insulin activity and action has continued. Currently, it is known that the role of insulin is much greater than simply regulating carbohydrate metabolism. Insulin in physiological concentration is also necessary to maintain normal vascular function. Insulin resistance is defined as a pathological condition characterized by reduced sensitivity of skeletal muscles, liver, and adipose tissue, to insulin and its downstream metabolic effects under normal serum glucose concentrations. There are also selective forms of insulin resistance with unique features, including vascular insulin resistance. Insulin resistance, both classical and vascular, contributes to vascular impairment resulting in increased risk of cardiovascular disease. Furthermore, in the elderly population, additional factors including redistribution of fat concentrations, low-grade inflammation, and decreased self-repair capacity [or cell senescence] amplify the vascular abnormalities related to insulin resistance.

The role of leptin and orexins in the dysfunction of hypothalamo-pituitary-gonadal regulation and in the mechanism of hyperactivity in patients with anorexia nervosa.

Anorexia nervosa (AN) belongs to a group of eating disorders and is characterized by extreme body weight loss. AN patients show combination of physical, psychological and behavioral disturbances. Neuropeptides partly control energy homeostasis and modulate hormone release. Leptin, a peptide secreted by adipocytes, may influence the interactions between central and peripheral signals. Hypoleptinaemia found in AN is connected with disturbed control of appetite and hormonal dysfunction as well as has implications for the hypothalamo-pituitary-gonadal axis, bone mineral density and physical hyperactivity. Low leptin levels are increased with refeeding. However, the prolonged hypoleptinaemia in weight recovered AN patients may result in persistent hypothalamic amenorrhoea. The hyperactivity has been observed in 31-80 % of AN cases. The mechanisms underlying the hyperactivity found in patients with anorexia nervosa seem to be more complicated as many factors including neuropeptides may be involved. Orexins may affect not only appetite but also behavior and psychophysical activity as they may regulate reproductive and stress hormone secretion, stimulate a variety of stereotypic behaviors including eating and stress reaction, and affect the hypothalamo-pituitary-adrenal (HPA) axis, alter glucocorticoid and catecholamine secretion and activate the sympathetic nervous system. Orexins influence the mechanism regulating arousal and sleep, cardiovascular function, temperature, metabolic rate and locomotive activity. It is worth considering how abnormal activity of hypothalamic neuropeptides or their receptors may play a role in the mechanisms of hyperactivity, disturbed control of appetite and hormonal dysfunction in patients with anorexia nervosa.

Involvement of the cocaine-amphetamine regulated transcript peptide (CART 55-102) in the modulation of rat immune cell activity.

OBJECTIVE: Cocaine-amphetamine regulated transcript peptides (CART) belong to a neuropeptide family expressed in the central nervous system, especially in the hypothalamus, and also in peripheral tissues. The physiological functions of CART include modulation of pituitary hormone release, regulation of body weight, and the control of feeding behavior and metabolic activity. The reciprocal relationships between CART and immune system function have to be established. Therefore, in the present study we aimed to investigate the influence of CART, administered intracerebroventricularly (icv), on selected immune parameters and pituitary-adrenal axis hormone secretion in the rat. RESEARCH METHODS: In rats submitted to icv infusion of CART or artificial cerebrospinal fluid (aCSF, control) selected immune parameters: splenocyte proliferation (spontaneous and mitogen-stimulated) and peritoneal leukocyte (PTL) activity (spontaneous and phorbol myristate acetate (PMA)-stimulated) were examined 60 and 120 min after treatment. The direct effect of CART on splenocytes in culture in vitro was also examined. Concentration of adrenocorticotrophic hormone (ACTH) and corticosterone was also measured in serum of control and CART infused rats. RESULTS: Splenocytes isolated 60 min after CART infusion exhibited a decreased, albeit non-significant, ability to proliferate spontaneously and were unable to answering to the mitogenic stimulation. This effect was not seen 120 min after CART treatment, which restored splenocyte proliferation decreased by aCSF infusion. CART addition in vitro did not influence proliferation of splenocytes from control rats. Spontaneous activity of peritoneal leukocytes was not modified by CART infusion. PMA-stimulated PTL activity was significantly decreased in aCSF-infused rats 120 min after treatment and CART infusion antagonized this effect. Non-significant increase in serum cortisol after 60 min followed by a significant decrease after 120 min with no change in ACTH concentration was found. CONCLUSION: The immunomodulatory activity of icv-infused CART appears to consist in the creation of a short-lasting immunosuppressive internal milieu, followed by the immunostimulatory one. This first effect was most probably due to the activation of the HPA axis and/or other immunosuppressive peptides, but not through the direct action of CART on immune cells. Thus, CART appears to be short-lasting and indirect modulator of immunity.

Plasma beta amyloid and cytokine profile in women with Alzheimer's disease.

Alzheimer's disease (AD) belongs to a group of neurodegenerative disorders. It is characterized by irreversible and progressive memory loss accompanied with decline in other cognitive functions. At a microscopic level, the typical neuropathologic features, senile plaques and neurofibrillary lesions are found. The pathological processes lead to neuronal loss, synaptic dysfunction and inappropriate activity of neurotransmitters. The major constituent of senile plaques is abnormally aggregated beta amyloid protein. Beta amyloid (Abeta) is a short (40-42 amino acid) product of proteolysis of the transmembrane amyloid precursor protein (APP). Extracellular depositions of Abeta 1-42 may initiate a wide range of pathological processes including glia activation, neuroinflammation and neuronal apoptosis. There is convincing evidence that inflammatory response to accumulation of beta amyloid plays a pivotal role in the progression of neuropathological changes found in AD. Current research was directed at assessing beta amyloid, cytokines (IL-6, IL-10 and TNF alpha) plasma levels in women with AD. Hundred and twenty four women, aged between 59 to 86 years, were enrolled in the study. Amongst them 57 were diagnosed with AD (29 subjects in early stage and 28 subjects with moderate to severe stadium of disease) and 67 women without dementia were investigated as a control group. The lowest values of Abeta 1-42 were found in AD subjects in moderate to severe stage of disease as compared with the early stage of AD (p< 0.05) and the control group (p<0.01). Change in IL-6 values was significantly different between groups with the lowest values found in women without dementia. Both subset of AD patients demonstrated statistically enhanced IL-6 levels when compared with the control group (p<0.001, p<0.01 respectively for early and moderate/severe stage of AD). Moreover, our study revealed a trend to increase in TNF alfa and IL-10 values in AD. However, those differences were not statistically significant. In addition, we did not detect any correlations between plasma beta amyloid and investigated cytokines.

Plasma adiponectin array in women with Alzheimer's disease.

Introduction Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. Typical features of AD include memory loss, social dysfunction and physical impairment. Although the pathological findings in the central nervous system are well established, the etiological factors are poorly known. Recent studies suggested the role of metabolic disturbances in the development of AD neurodegeneration. Adiponectin, an anti-inflammatory and metabolism regulating factor, was linked to AD. Aim The aim was to examine whether adiponectin fractions combined with insulin/insulin resistance-associated metabolic parameters correlate with AD progression. Material and methods The study comprised 98 women: 27 with moderate to severe AD, 31 with AD at early stage and 40 healthy controls, matched for age and BMI. To evaluate memory impairment, the MMSE was performed. Plasma total adiponectin and its high-, medium- and low molecular weights were measured with ELISA. Anthropometric, clinical and metabolic parameters were assessed. Correlations between adiponectin array and measured parameters were evaluated. Results In comparison to the controls, enhanced levels of total and medium molecular weight adiponectin characterized AD individuals. In AD, we found correlations between adiponectin array, and anthropometric and biochemical parameters. After adjustment to BMI, a significant increase of the total adiponectin and high- and medium molecular weight fractions was observed. A negative correlation between low molecular weight adiponectin and MMSE was found. Conclusions Our results indicate a possible link between adiponectin variations and AD. We hypothesize that changes in adiponectin profile observed in AD result from compensatory mechanism against neuropathological processes, as well as from adiponectin homeostasis impairment.

PACAP 38 inhibits adiponectin release.

BACKGROUND: Pituitary adenylate cyclase activating peptide (PACAP 38) is a neuropeptide with anti-inflammatory activity. Vasoactive intestinal peptide (VIP)/PACAP receptors are found in immune cells, endocrine glands and also in adipose tissue. Adiponectin is an adipocyte-derived protein hormone which possesses anti-inflammatory, antidiabetic and antiatherogenic properties. The aim of this study was to examine the influence of PACAP 38 on adiponectin release in basal conditions and during lipopolysaccharide (LPS)-induced acute inflammation. METHODS: Male Wistar-Kyoto rats were divided into four groups which received intraperitoneal injections of 0.9% NaCl, LPS, PACAP 38 or LPS+PACAP 38, respectively. Serum adiponectin concentrations were measured using an ELISA test. RESULTS: LPS administration did not change adiponectin concentration; however, PACAP 38 administered alone decreased serum adiponectin concentration after 2 h (p<0.05) and 4 h (p<0.01). In the group that received LPS+PACAP38, compared with LPS alone, no difference in adiponectin concentration was observed. CONCLUSIONS: We conclude that PACAP 38 may directly modulate adiponectin secretion by adipocytes in basal conditions.