The Role of Adipokines and Myokines in the Pathogenesis of Different Obesity Phenotypes-New Perspectives.

Obesity is a characteristic disease of the twenty-first century that is affecting an increasing percentage of society. Obesity expresses itself in different phenotypes: normal-weight obesity (NWO), metabolically obese normal-weight (MONW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). A range of pathophysiological mechanisms underlie the occurrence of obesity, including inflammation, oxidative stress, adipokine secretion, and other processes related to the pathophysiology of adipose tissue (AT). Body mass index (BMI) is the key indicator in the diagnosis of obesity; however, in the case of the NWO and MONW phenotypes, the metabolic disturbances are present despite BMI being within the normal range. On the other hand, MHO subjects with elevated BMI values do not present metabolic abnormalities. The MUO phenotype involves both a high BMI value and an abnormal metabolic profile. In this regard, attention has been focused on the variety of molecules produced by AT and their role in the development of obesity. Nesfatin-1, neuregulin 4, myonectin, irisin, and brain-derived neurotrophic factor (BDNF) all seem to have protective effects against obesity. The primary mechanism underlying the action of nesfatin-1 involves an increase in insulin sensitivity and reduced food intake. Neuregulin 4 sup-presses lipogenesis, decreases lipid accumulation, and reduces chronic low-grade inflammation. Myonectin lowers the amount of fatty acids in the bloodstream by increasing their absorption in the liver and AT. Irisin stimulates the browning of white adipose tissue (WAT) and consequently in-creases energy expenditure, additionally regulating glucose metabolism. Another molecule, BDNF, has anorexigenic effects. Decorin protects against the development of hyperglycemia, but may also contribute to proinflammatory processes. Similar effects are shown in the case of visfatin and chemerin, which may predispose to obesity. Visfatin increases adipogenesis, causes cholesterol accumulation in macrophages, and contributes to the development of glucose intolerance. Chemerin induces angiogenesis, which promotes the expansion of AT. This review aims to discuss the role of adipokines and myokines in the pathogenesis of the different obesity phenotypes.

Does gut microbiota affect the success of weight loss? Evidence and speculation.

Obesity is a chronic state of excessive fat accumulation in the body, characterized by significant relapse and complicated by a range of health consequences. In the treatment of obesity, a holistic approach including diet, physical activity, pharmacotherapy, bariatric surgery, and psychological support is recommended. The implications of gut microbiota (GM) as a pathogenic factor in excess body weight have been discussed, and microbial-targeted therapies-including probiotics, prebiotics, and synbiotics-are considered adjuvant in obesity management. Many studies have focused on assessing the effectiveness of probiotics, prebiotics, or synbiotics in weight control, although with inconclusive results, mainly because of the significant heterogeneity of the studies (with different strains, doses, forms, interventional durations, and outcomes). It is also unclear whether using probiotics or synbiotics accompanied by weight loss dietary interventions or as a part of bariatric surgery will be more effective in obesity management, not only in the short-term but also for long-term weight loss maintenance. The aim of this study was to collect and compare the available scientific data on the effectiveness of probiotic or synbiotic supplementation (as a single therapy versus as part of dietary interventions, pharmacotherapy, or bariatric therapy) on weight control in obesity.

The Preventive Mechanisms of Bioactive Food Compounds against Obesity-Induced Inflammation.

Dietary patterns are promising strategies for preventing and treating obesity and its coexisting inflammatory processes. Bioactive food compounds have received considerable attention due to their actions against obesity-induced inflammation, with limited harmful side effects. They are perceived as food ingredients or dietary supplements other than those necessary to meet basic human nutritional needs and are responsible for positive changes in the state of health. These include polyphenols, unsaturated fatty acids, and probiotics. Although the exact mechanisms of bioactive food compounds' action are still poorly understood, studies have indicated that they involve the modulation of the secretion of proinflammatory cytokines, adipokines, and hormones; regulate gene expression in adipose tissue; and modify the signaling pathways responsible for the inflammatory response. Targeting the consumption and/or supplementation of foods with anti-inflammatory potential may represent a new approach to obesity-induced inflammation treatment. Nevertheless, more studies are needed to evaluate strategies for bioactive food compound intake, especially times and doses. Moreover, worldwide education about the advantages of bioactive food compound consumption is warranted to limit the consequences of unhealthy dietary patterns. This work presents a review and synthesis of recent data on the preventive mechanisms of bioactive food compounds in the context of obesity-induced inflammation.

Association of Serum Vaspin Concentration with Metabolic Disorders in Obese Individuals.

Vaspin, a molecule produced in visceral adipose tissue, seems to participate in the pathogenesis of metabolic disorders. The study aimed to determine the association of vaspin concentration with metabolic disorders in obese individuals. Forty obese patients and twenty normal-weight subjects underwent biochemical (fasting glucose, insulin, lipid profile, interleukin-6, hs-CRP, vaspin concentration), blood pressure, and anthropometric measurements. The HOMA-IR index was calculated. Serum vaspin concentrations in the obese group were significantly higher than in the control group (0.82 ± 0.62 vs. 0.43 ± 0.59; p < 0.001). Among the entire population, vaspin concentration was positively correlated with body weight, BMI, WHR, and the percentage and mass of adipose tissue. Positive correlations between vaspin concentration and triglyceride level, insulin concentration, and HOMA-IR value were found. Vaspin concentration was positively correlated with hs-CRP and IL-6 levels. In obese patients, positive correlations between vaspin concentration and the percentage of adipose tissue and hs-CRP level were demonstrated. Logistic regression analysis showed that increased BMI was the biggest factor stimulating vaspin concentrations (OR = 8.5; 95% CI: 1.18-61.35; p = 0.0338). An elevated vaspin level may imply its compensatory role against metabolic disorders in obese patients. Thus, vaspin appears to be a useful diagnostic parameter for new therapeutic approaches in obesity-related complications. Nevertheless, due to the small sample size, further studies are needed to confirm our results.

Association of Serum Omentin-1 Concentration with the Content of Adipose Tissue and Glucose Tolerance in Subjects with Central Obesity.

Omentin is one of the few adipokines with potentially beneficial metabolic effects. The main aim of this study was to determine the association between serum omentin-1 levels and the occurrence of central obesity and abnormal glucose tolerance, taking into account gender. The study involved 88 participants aged 30-60, including 47 women and 41 men. Two subgroups among the obese subjects were distinguished-those with normal and abnormal glucose tolerance. Anthropometric and biochemical examinations and blood pressure measurements were performed. Omentin-1 concentrations were significantly lower among patients with obesity compared to those without obesity (p = 0.027) and, similarly, comparing men with abnormal glucose tolerance with men with normal glucose tolerance (p = 0.035). In contrast, no such pattern was observed in women. The multivariable regression model showed a significant effect of gender status and important factors of tissue insulin sensitivity, such as OGGT results, WHR and amount of body fat, on the variability of serum omentin-1 concentration in the entire study population (R2adj. = 13.7%; p = 0.003). High omentin-1 levels found in men with obesity and normal glucose tolerance suggest that omentin-1 protects against metabolic disorders associated with obesity in the male population.

The Role of Magnesium in the Pathogenesis of Metabolic Disorders.

Magnesium (Mg) is an essential nutrient for maintaining vital physiological functions. It is involved in many fundamental processes, and Mg deficiency is often correlated with negative health outcomes. On the one hand, most western civilizations consume less than the recommended daily allowance of Mg. On the other hand, a growing body of evidence has indicated that chronic hypomagnesemia may be implicated in the pathogenesis of various metabolic disorders such as overweight and obesity, insulin resistance (IR) and type 2 diabetes mellitus (T2DM), hypertension (HTN), changes in lipid metabolism, and low-grade inflammation. High Mg intake with diet and/or supplementation seems to prevent chronic metabolic complications. The protective action of Mg may include limiting the adipose tissue accumulation, improving glucose and insulin metabolism, enhancing endothelium-dependent vasodilation, normalizing lipid profile, and attenuating inflammatory processes. Thus, it currently seems that Mg plays an important role in developing metabolic disorders associated with obesity, although more randomized controlled trials (RCTs) evaluating Mg supplementation strategies are needed. This work represents a review and synthesis of recent data on the role of Mg in the pathogenesis of metabolic disorders.

The Effect of Artificial Sweeteners Use on Sweet Taste Perception and Weight Loss Efficacy: A Review.

Excessive consumption of sugar-rich foods is currently one of the most important factors that has led to the development of the global pandemic of obesity. On the other hand, there is evidence that obesity contributes to reduced sensitivity to sweet taste and hormonal changes affecting appetite, leading to an increased craving for sweets. A high intake of sugars increases the caloric value of the diet and, consequently, leads to weight gain. Moreover, attention is drawn to the concept of the addictive properties of sugar and sugary foods. A potential method to reduce the energy value of diet while maintaining the sweet taste is using non-nutritive sweeteners (NNS). NNS are commonly used as table sugar substitutes. This wide group of chemical compounds features high sweetness almost without calories due to its high sweetening strength. NNS include aspartame, acesulfame-K, sucralose, saccharin, cyclamate, neohesperidin dihydrochalcone (neohesperidin DC), neotame, taumatin, and advantame. The available evidence suggests that replacing sugar with NNS may support weight control. However, the effect of NNS on the regulation of appetite and sweet taste perception is not clear. Therefore, the review aimed to summarize the current knowledge about the use of NNS as a potential strategy for weight loss and their impact on sweet taste perception. Most studies have demonstrated that consumption of NNS-sweetened foods does not increase sweetness preference orenergy intake. Nonetheless, further research is required to determine the long-term effects of NNS on weight management.

The Association of Serum Circulating Neuropeptide Q and Chemerin Levels with Cardiometabolic Risk Factors among Patients with Metabolic Syndrome.

The potential involvement of neuropeptide Q (NPQ) and chemerin (CHEM) in metabolic disorders is yet to be fully elucidated. The aim of this study was to evaluate serum concentrations of NPQ and CHEM and to establish their relationship with cardiometabolic risk factors among individuals with metabolic syndrome. A total of 66 patients with metabolic syndrome (MetS) and 83 healthy volunteers (non-MetS) underwent biochemical, blood pressure, and anthropometric measurements. The concentration of NPQ in the MetS group was significantly lower (0.47 (0.34 ; 0.54) vs. 0.52 (0.43 ; 0.60) ng/mL, p = 0.015) than in non-MetS, while there were no differences in CHEM level. In the entire study population, we observed several negative correlations between NPQ concentration and waist-hip ratio (WHR), visceral adipose tissue, diastolic blood pressure (DBP), triglycerides (TG) along with a positive correlation with high-density lipoprotein (HDL), total muscle mass, and CHEM. Moreover, a negative correlation was observed in the MetS group between NPQ and glycemia. CHEM showed no significant correlations with cardiometabolic risk factors in the study population. In a multiple regression model, the total muscle mass proved to be an independent factor determining NPQ concentration in the population (p < 0.00000001, R2adj = 28.6%). NPQ seems to protect against metabolic disorders correlated with obesity. Thus, it is worth considering NPQ level as a candidate protective biomarker of metabolic syndrome complications.

Assessment of Selected Clock Proteins (CLOCK and CRY1) and Their Relationship with Biochemical, Anthropometric, and Lifestyle Parameters in Hypertensive Patients.

BACKGROUND: Circadian rhythms misalignment is associated with hypertension. The aim of the study was to evaluate the concentration of selected clock proteins-cryptochrome 1 (CRY1) and circadian locomotor output cycles kaput (CLOCK) to determine their relationships with biochemical and anthropometric parameters and lifestyle elements (diet, physical activity, and quality of sleep) in hypertensive patients. METHODS: In 31 females with hypertension (HT) and 55 non-hypertensive women (NHT) the CRY1 and CLOCK concentrations, total antioxidant status (TAS), lipid profile, and glycemia were analyzed. Blood pressure and anthropometric measurements, nutritional, exercise, and sleep analyses were performed. RESULTS: In the HT group, the CRY1 level was 37.38% lower than in the NHT group. No differences were noted in CLOCK concentration between groups. BMI, FBG, and TG were higher in the HT group compared to the NHT group, while TC, LDL, and HDL levels were similar. The study showed no relationship between CRY1 or CLOCK concentrations and glucose or lipids profile, amount of physical activity, or sleep quality, although CRY1 was associated with some anthropometric indicators. In the HT group, increased CLOCK and CRY1 values were associated with a high TAS level. CONCLUSIONS: The serum level of CRY1 could be considered in a detailed diagnostic of hypertension risk in populations with abnormal anthropometric indices.

The effect of Plantago major supplementation on leptin and VEGF-A serum levels, endothelial dysfunction and angiogenesis in obese women - a randomised trial.

Obesity is associated with increased serum leptin level, endothelial dysfunction and angiogenesis. In vitro studies have shown that vascular endothelial growth factor (VEGF) synthesis is increased by leptin. Animal studies revealed the effectiveness of Plantago supplementation treatment of obesity. The study aim was to evaluate the effect of Plantago major supplementation on serum leptin and VEGF blood concentration, endothelial dysfunction and angiogenesis in obese women. Seventy-two obese women received oral Plantago major supplement (Plantago group, n = 35) or placebo (placebo group, n = 37) for 12 weeks. At baseline and after completion, anthropometric and body composition measurements were performed, and blood samples were collected. Serum concentrations of leptin, VEGF-A, adiponectin, tumour necrosis factor α and soluble intercellular adhesion molecule have been determined. At completion, the leptin level was higher in the Plantago group (39 781.55 ± 20 360.73 pg ml-1) compared to both the baseline (36 138.71 ± 25 401.51 pg ml-1) and placebo group (30 502.81 ± 19 003.18 pg ml-1). Also, leptin concentration in the Plantago group at completion correlated positively with an increase in VEGF-A level (R = 0.45), and baseline VEGF-A level correlated negatively with the increase in leptin concentration (R = -0.47). Plantago major supplementation increases leptin serum level, enhances leptin influence on VEGF-A serum level increase and by this mechanism may intensify endothelial dysfunction and angiogenesis in obese women.

Association of serum omentin concentration with anthropometric, physiological, and biochemical parameters in obese individuals.

OBJECTIVE: Omentin is a secretory protein produced in visceral adipose tissue. The potential protective action of omentin in metabolic disorders is not yet fully understood. The aim of this study was to determine the association of omentin with anthropometric, physiologic, and biochemical parameters in obese individuals. METHODS: Sixty obese individuals and 40 normal weight controls were enrolled in the study. Anthropometric measurements were taken, systolic (SBP) and diastolic blood pressures (DBP) were recorded. Serum fasting glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), lipid profile, and serum omentin concentrations were determined. RESULTS: The concentration of omentin in obese individuals was significantly lower than in controls (145.5 ± 33.3 versus 383.6 ± 92.9; P < 0.001). Omentin correlated negatively with waist circumference (P < 0.01), hip circumference (P < 0.05), percent of adipose tissue (P < 0.001), fasting insulin (P < 0.001), HOMA-IR (P < 0.001), and SBP (P < 0.001) in the patients who were obese. A positive relationship was documented with high-density lipoprotein in both the obese patients (P < 0.01) and the overall population (P < 0.001). Multiple negative omentin correlations with body weight, body mass index, waist and hip circumference and its ratio, percent of adipose tissue, SBP, triacylglycerols, glucose, fasting insulin, and HOMA-IR were demonstrated in the entire population. In the multivariate linear regression model, insulin concentration (ß = -0.49; P < 0.001), percent of adipose tissue (ß = -0.31; P < 0.001), and waist circumference (ß = -0.21; P < 0.01) were independent predictors of omentin concentration in individuals who were obese. CONCLUSIONS: A concentration of omentin is associated with cardiometabolic risk-related factors in obesity. Fasting insulin, adipose tissue percentage, and waist circumference can be considered candidates for markers of omentin concentration in obese individuals.

Evaluation of Vitamin D Fractions in Obese Hypertensive Patients.

Vitamin D fractions can be involved in the pathogenesis of metabolic disorders, but their concentrations are rarely determined. The aim of this study was to evaluate the concentration of vitamin D fractions in obese hypertensive patients and to determine its associations with anthropometric parameters, glucose levels, and lipid profiles. A total of 85 obese hypertensive patients (OBHT) and 40 nonobese nonhypertensive subjects (NOBNHT) underwent biochemical measurements of lipid profiles, glycemia, 25-hydroxyvitamin D (25(OH)D), free vitamin D (free25(OH)D), vitamin D binding protein, albumin levels. Moreover, free25(OH)D and bioavailable25(OH)D (bio25(OH)D) concentrations were calculated. Blood pressure and anthropometric measurements were performed. Differences between groups (p < 0.001) were found for 25(OH)D (OBHT 40.25 ± 18.02 vs. NOBNHT 64.10 ± 22.29 nmol/L), free25(OH)D (9.77 (7.46; 11.49) vs. 13.80 (10.34; 16.82) pmol/L), bioavailable 25(OH)D (3.7 (2.8; 4.4) vs. 5.4 (4.2; 6.7) nmol/L), and calculated free25(OH)D (7.82 (5.54; 11.64) vs. 10.46(8.06;16.28) pmol/L, p = 0.002). The OBHT patients showed no relationship between vitamin D fractions concentration and glucose or lipids level, although it was associated with anthropometric parameters. In the NOBNHT group, vitamin D fractions correlated positively with HDL cholesterol and negatively with triglyceridemia and hip circumference. Vitamin D fractions were decreased in obese hypertensive subjects, and were associated with anthropometric parameters, but not with glucose level or lipid profiles; they thus cannot be considered as a predictive marker of metabolic disorders in this group of patients.

Neuropeptide B and neuropeptide W as new serum predictors of nutritional status and of clinical outcomes in pediatric patients with type 1 diabetes mellitus treated with the use of pens or insulin pumps.

INTRODUCTION: The aim of our study was to determine the relationship between neuropeptide B (NPB), neuropeptide W (NPW), nutritional and antioxidant status and selected fat- and bone-derived factors in type 1 diabetes mellitus (T1DM) treated using pens (T1DM pen group) or insulin pumps (T1DM pump group) in order to investigate the potential role of NPB and NPW in the clinical outcomes of T1DM. MATERIAL AND METHODS: Fifty-eight patients with T1DM and twenty-five healthy controls (CONTR) participated in the study. Assessments of NPB, NPW, total antioxidant status (TAS), leptin, adiponectin, osteocalcin, and free soluble receptor activator for nuclear factor κB (free sRANKL) were conducted. RESULTS: NPB, NPW, leptin, and TAS were lower (by 33%, p < 0.013; 34%, p < 0.008; 290%, p < 0.00004; 21%, p < 0.05; respectively), while adiponectin was by 51% higher (p < 0.006) in T1DM vs. CONTR, while osteocalcin and free sRANKL levels were similar in both groups. NPW was lower in the T1DM pen group both vs. the T1DM pump group (36% lower, p < 0.0009) and vs. the CONTR group (35% lower, p < 0.002). In the T1DM pen group, but not in the T1DM pump group or the CONTR group, the Cole index and TAS levels explain (besides NPB) the variation in NPW values. ROC curves showed that serum levels of leptin, adiponectin, NPB and NPW (but not osteocalcin or free sRANKL) were predictive indicators for T1DM. CONCLUSIONS: Measurements of NPB and NPW, besides leptin and adiponectin, are worth considering in the detailed prognosis of nutritional status in T1DM, primarily in the T1DM pen-treated population.

Impact of 25-hydroxyvitamin D, free and bioavailable fractions of vitamin D, and vitamin D binding protein levels on metabolic syndrome components.

INTRODUCTION: Various forms of vitamin D and factors involved in their metabolism can play a role in the etiopathogenesis of metabolic disorders. This paper aims to define the relationship between concentration of the hydroxylated form of vitamin D (25(OH)D), the fraction of free and bioavailable vitamin D, and of vitamin D binding protein (VDBP) levels on the one hand and the prevalence of metabolic syndrome components on the other. MATERIAL AND METHODS: The studies were conducted on 79 people, including 52 with metabolic syndrome (MetS+) and 27 without it (MetS-). Biochemical measurements (lipid profile, glycemia, 25(OH)D, VDBP, albumin, calcium, parathyroid hormone) were performed, concentration of free and bioavailable vitamin D was mathematically calculated, and anthropometric and blood pressure measurements were taken. RESULTS: The mean ± SD concentration of 25(OH)D among MetS+ individuals (41.90 ±13.12 nmol/l) was lower (p < 0.0001) than among the MetS- group (66.09 ±18.02 nmol/l). Differences between groups were observed in relation to medians/means of concentrations of free and bioavailable vitamin D (p < 0.0001) but not in the case of VDBP. In the entire study population, 25(OH)D correlated with all metabolic syndrome components, whereas its free and bioavailable fraction correlated with particular components of the syndrome. In the MetS+ group, VDBP concentration negatively correlated with body mass index (p = 0.037) and levels of diastolic pressure (p = 0.022). In the case of the MetS- group, the free fraction of vitamin D negatively correlated with triglyceridemia (p = 0.049). CONCLUSIONS: The evaluation of various forms of vitamin D and VDBP in different population groups seems to have significant clinical value in evaluating the prevalence of metabolic disorders.

Hypovitaminosis D and adipose tissue - cause and effect relationships in obesity.

In recent years, attention has been focused on pleiotropic directions of effects exerted by vitamin D. Epidemiological data indicate that deficiency of vitamin D in various population groups represents an increasingly widespread phenomenon, while a decreased serum concentration of calcitriol correlates with manifestation of civilization-linked diseases, including visceral obesity. This study aims at a review and synthesis of data linked to relationships between lowered vitamin D concentrations in blood and manifestation of obesity, and potential mechanisms which affect the concentration of the vitamin in conditions of an excessive accumulation of adipose tissue. Several variables are distinguished which can affect the status of vitamin D in obesity, but the key role in this respect is ascribed to the metabolic activity of visceral adipose tissue. Among others, the activity favours sequestration and modulation of calcitriol turnover. On the other hand, the effects of vitamin D on the process of adipogenesis and its involvement in remodelling of adipose tissue are pointed out. Also, several factors of an environmental nature (e.g. time of year/day, dietetic supply of vitamin D), genetic nature (e.g. genetic polymorphisms) and other conditioning (e.g. coexisting diseases, age, content of melanin in skin) cannot be bypassed as they may affect the concentration of vitamin D. Nevertheless, it still remains unresolved to what extent hypovitaminosis D represents the cause and to which it is the effect of obesity.

Concentrations of omentin and vaspin versus insulin resistance in obese individuals.

INTRODUCTION: Omentin and vaspin are adipokines manifesting a potentially protective action against obesity-associated metabolic disturbances. AIM: Evaluation of relationship between serum concentrations of omentin and vaspin on one hand and indices of insulin resistance and anthropometric parameters in obese individuals on the other. MATERIAL AND METHODS: The studies were conducted on 64 individuals. The investigated group (37 obese patients) included the subgroup with normal glucose tolerance (NGT) and with abnormal glucose tolerance (AGT). The control group (n=27) included healthy individuals with normal body weight. In all participants anthropometric analyses and biochemical tests, including estimation of omentin and vaspin concentrations were performed, and insulin resistance by HOMA-IR was evaluated. RESULTS: Concentrations of examined adipokines manifested no significant differences between the examined groups. Median values of the index defining ratio between studied adipokine and degree of insulin resistance, i.e. omentin/HOMA-IR, proved to be different in the investigated and the control group while no such difference could be noted in cases of vaspin/HOMA-IR indices. In the studied population a negative relationship was detected between serum concentration of omentin and systolic blood pressure (p<0.04). Values of omentin/HOMA-IR index manifested a correlation with values of most anthropometric parameters (p<0.0001), blood pressure (p<0.0001) concentrations of TG (p<000.1) and HDL (p<0.0001), ISIbasal (p<0.00001), ISIgly (p<0.0001), Quicki (p<0.00001) and fasting insulinaemia (p<0.00001). In the case of vaspin/HOMA-IR index only its positive relationship with HDL concentration was noted (p<0.05). CONCLUSION: In context of date of correlation, multiple regression and values of area of under receiver operating characteristics curve omentin, as compared to vaspin, seems to provide a better predictor of insulin resistance in obese individuals.