Aziz Aksoy

Today's and yesterday's of pathophysiology: Biochemistry of metabolic syndrome and animal models

During the past 20 y, there has been much interest in sugars and especially fructose in relation to human health. Over the past decade, considerable scientific debate and controversy have arisen about the potential health effects of sucrose, high-fructose corn syrup (HFCS), and fructose itself. HFCS increasingly has been used as a sweetener in thousands of food products and soft drinks, leading to the development of obesity, diabetes, dyslipidemia, and metabolic syndrome (MetS) in both rodents and humans, which is associated with an increase in body weight. There is a need for detailed research on the mechanism underlying MetS that could lead to a remedy. This review will first systematically present a definition of MetS, its history, prevalence, and comparative diagnostic criteria. We will then consider fructose and its effects on human health, the diet-induced obesity model (various fat contents), the hypercholesterolemic model, the diabetes model, the hypertensive model, the MetS or insulin resistance model, and biomarkers related to MetS, in light of contemporary data using multiple databases (PubMed, MEDLINE, and OVID).

Regulatory neuropeptides (ghrelin, obestatin and nesfatin-1) levels in serum and reproductive tissues of female and male rats with fructose-induced metabolic syndrome

Although, the exact mechanisms underlying the development of the metabolic syndrome (MetS) are not still completely understood, obesity, circulated peptide hormone levels and their interaction with genetic factors are considered largely responsible. The purpose of this study is to explore how the levels of ghrelin, obestatin (OBS) and NUCB2/nesfatin-1 (NES)/NUCB2 change in serum and the reproductive tissues of female and male rats with fructose-induced metabolic syndrome, and whether the levels of each hormone is correlated with the hormones involved with fertility. Experiments were conducted on 5-week-old Sprague-Dawley male and female rats assigned to either a control group or a MetS group. Controls were fed standard rat food and water ad libitum, while the MetS group was fed standard food with 10% (v/v) fructose solution added to their drinking water for 12 weeks with a 12/12h photoperiod circle. Then, all animals were sacrificed after a one night fast. Peptides levels in the serum and reproductive tissues of rats were studied using the ELISA method while the immunoreactivity of reproductive system peptide hormones were shown by immunohistochemical staining method. Furthermore, the other biochemical parameters were measured using Konelab-60 equipment and infertility hormones were measured with Immulite2000. Fasting serum insulin, glucose, triglyceride, alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) levels were statistically significantly higher, and the amount of high density lipoprotein cholesterol (HDL-C) was significantly lower, in the MetS groups. Serum and tissue supernatant NES levels were significantly higher in the rats with MetS than the control group. Ghrelin, OBS and NES were expressed in the cytoplasm, concentrated around the apical parts of the epithelial cells in the reproductive tissues of the rats. The amounts of ghrelin were lower in the reproductive tissues of the animals with MetS, while NES levels in the same tissues increased. Obestatin also decreased, though not in the seminal glands.

Changes in serum obestatin, preptin and ghrelins in patients with Gestational Diabetes Mellitus.

OBJECTIVES The present study aims to establish the levels of acylated ghrelin, desacylated ghrelin, obestatin and preptin, during pregnancy and the postpartum period in pregnant women with Gestational Diabetes Mellitus (GDM) and healthy pregnancy women. DESIGN AND METHODS The study registered 20 pregnant women with GDM and 20 healthy pregnant women. Fasting venous blood samples were collected from all cases between weeks 24 and 28 of pregnancy and after 24h postpartum. Hormones were analyzed using ELISA method. RESULTS Serum acylated ghrelin (p:0.001), desacylated ghrelin (p:0.001), obestatin (p:0.006) and preptin (p:0.001) levels were all found statistically higher in both groups during the postpartum period, when compared to the pregnancy period. A positive correlation was established between desacylated ghrelin and acylated ghrelin (p:0.008), desacylated ghrelin and preptin (p:0.012) and preptin and insulin (p:0.039) in the GDM group during pregnancy. CONCLUSIONS The studied hormones (especially desacylated ghrelin and obestatin) are critical in GDM pathophysiology based on the comparison of measure after and before the delivery.

Concentrations of preptin, salusins and hepcidins in plasma and milk of lactating women with or without gestational diabetes mellitus

This study was undertaken to ascertain whether human milk contains preptin, salusin-alpha (salusin-α) and -beta (salusin-β) and pro-hepcidin and hepcidin-25, and whether there are relationships between plasma and milk preptin, salusin-α and -β and pro-hepcidin and hepcidin-25 concentrations in lactating mothers with and without gestational diabetes mellitus (GDM). Blood was obtained from non-lactating women (n = 12), non-diabetic lactating women (n = 12), and GDM lactating women (n = 12). Colostrum, transitional milk, and mature milk samples were collected just before suckling from healthy and GDM lactating women. Peptides concentrations were determined by ELISA and EIA. Mammary gland tissues were screened immunohistochemically for these peptides. Women with GDM had significantly higher plasma and colostum preptin concentrations than healthy lactating women during the colostral and transitional milk period. Salusin-alpha and -beta levels in milk and plasma were lower in women with GDM. Salusin-α and -β were significantly lower in both plasma and colostrums of GDM than of healthy lactating women. Women with GDM had significantly higher colostum prohepcidin and hepcidin-25 concentrations than healthy lactating women during the colostral period. Plasma prohepcidin was also higher in women with GDM than in healthy lactating women during the colostral period, but plasma prohepcidin and hepcidin-25 levels decreased during mature milk period. Transitional milk pro-hepcidin and hepcidin-25 levels in women with GDM were higher than in healthy lactating women. All these results revealed that the mammary gland produces those peptides, which were present in milk at levels correlating with plasma concentrations.

Ghrelins, obestatin, nesfatin-1 and leptin levels in pregnant women with and without hyperemesis gravidarum

OBJECTIVES The goal of this study was to compare levels of acyl and des-acyl ghrelin, obestatin, nesfatin-1 and leptin in healthy gravidas to hyperemesis gravidarum (HG) patients. DESIGN AND METHODS Twenty pregnant women with HG and twenty healthy pregnant women all of similar ages, BMI and all at similar pregnancy development comprised the study cohort. Fasting serum samples were obtained and measured for acyl and des-acyl ghrelin, leptin, obestatin and nesfatin-1. RESULTS Nesfatin-1 concentrations in the HG group were higher compared to the control group whereas; leptin concentrations during pregnancy were lower in the HG group as compared to the control group. The two groups did not differ with regard to acyl and des-acyl ghrelin and obestatin. CONCLUSION This pilot study suggests a possible role of leptin and nesfatin-1, which might be involved in the pathology of the disease.

Acylated and Desacylated Ghrelin, Preptin, Leptin, and Nesfatin-1 Peptide Changes Related to the Body Mass Index

This study examines the levels of acylated and desacylated ghrelin, preptin, leptin, and nesfatin-1 peptide changes related to the body mass index (BMI). The subjects were allocated to 5 groups depending on their BMIs as follows: Group I (BMI <18.5 kg/m2); Group II (BMI 18.5–24.9 kg/m2); Group III (BMI 25–29.9 kg/m2); Group IV (BMI 30–39.9 kg/m2); Group V (BMI >40 kg/m2). Serum acylated and desacylated ghrelin, preptin, and leptin levels were measured by the enzyme-linked immunosorbent assay (ELISA) and nesfatin-1 was measured by the enzyme immunoassay (EIA). Desacylated ghrelin levels showed a gradual and statistically significant drop from Group I to Group V, while preptin and leptin levels exhibited a gradual and significant increase from Group I to Group IV. Serum nesfatin-1 levels gradually, but not significantly, increased from Group I to Group III and showed a significant decrease in Groups IV and V. In conclusion, leptin, preptin, and acylated ghrelin (AG) levels increased with higher BMI, whereas desacylated ghrelin (DAG) decreased and nesfatin-1 showed no clear relationship to BMI.

The Past and Present of Paraoxonase Enzyme: Its Role in the Cardiovascular System and Some Diseases

The Past and Present of Paraoxonase Enzyme: Its Role in the Cardiovascular System and Some Diseases Although paraoxonase is synthesized in many tissues including the heart, colon, kidneys, lungs, small intestines and brain, its major locus of synthesis is the liver. PON1 is in close association with apolipoproteins and protects LDL against oxidation. It was reported that PON1 quantities dropped to 40 times lower than normal in cardiovascular diseases and diseases like diabetes, ulcerative colitis, Crohns disease, chronic renal failure, SLE, Behcets disease, cancer, hepatitis B, obesity, metabolic syndrome, Alzheimers and dementia. It is speculated that the concerning decline in serum PON1 amount results from single nucleotide polymorphism in the coding (Q192R, L55M) and promoter (T-108C) sites of the PON1 gene. Additionally, circulating amounts of PON1 are affected by vitamins, antioxidants, fatty acids, dietary factors, drugs, age and lifestyle. This collection attempts to review and examine the past and present studies of paraoxonase and its relation with the cardiovascular system and some relevant diseases. Prošlost i Sadašnjost Enzima Paraoksonaze: Njena Uloga u Kardiovaskularnom Sistemu i Nekim Bolestima Iako se paraoksonaza sintetiše u mnogim tkivima, uključujući srce, debelo crevo, bubrege, pluća, tanko crevo i mozak, glavno mesto njene sinteze je jetra. PON1 je blisko povezana sa apolipoproteinima i štiti LDL od oksidacije. Količine PON1 čak 40 puta niže od normalnog nivoa zabeležene su u kardiovaskularnim bolestima i oboljenjima kao što su dijabetes, ulcerozni kolitis, Kronova bolest, hronična bubrežna insuficijencija, sistemski eritemski lupus, Behčetov sindrom, kancer, hepatitis B, gojaznost, metabolički sindrom, Alchajmerova bolest i demencija. Spekuliše se da pomenuti pad nivoa PON1 u serumu potiče od polimorfizma pojedinačnih nukleotida na kodnim (Q192R, L55M) i promoterskim (T-108C) područjima gena PON1. Pored toga, na količinu PON1 u cirkulaciji utiču vitamini, antioksidansi, masne kiseline, faktori ishrane, lekovi, godine i način života. Ovaj pregled predstavlja pokušaj da se izlože i razmotre prošle i sadašnje studije o paraoksonazi i njenom odnosu sa kardiovaskularnim sistemom i nekim relevantnim bolestima.

Comparison of the therapeutic effects of sildenafil citrate, heparin and neuropeptides in a rat model of acetic acid-induced gastric ulcer

Aims: The purpose of our investigative work has been to determine whether there can be therapeutic roles in the administration of sildenafil citrate, heparin and several neuropeptides on an animal model where gastric ulcers were induced with acetic acid, and to compare their efficacy. Materials and methods: The animals were divided into 13 groups, with 4 animals in each. Gastric ulcers was induced in the animals of 12 groups with one untreated group being left as the control (Group I ‐ control; given normal saline (NS)). The other groups were: Group II (ulcer + NS); Group III (5 mg/kg sildenafil citrate, low dose); Group IV (10 mg/kg sildenafil citrate, high dose); Group V (0.6 mg/kg heparin, low dose); Group VI (6 mg/kg heparin, high dose); Group VII (20 nmol/kg des‐acyl ghrelin); Group VIII (40 nmol/kg des‐acyl ghrelin); Group IX (4 nmol/kg acyl ghrelin); Group X (8 nmol/kg acly ghrelin); Group XI (20 pmol/kg Nesfatin‐1); Group XII (15 nmol/kg Obestatin) and Group XIII (5 nmol/kg Neuropeptide Y). Gastric neuropeptide expression was measured using an immunohistochemical method, and the amount in circulation was detected using ELISA. To compare with no treatment, the controls and other treatment groups, we recorded loss of the surface epithelium of the stomach, erosion, bleeding and inflammatory cell infiltration in the upper halves of the gastric glands. Key findings: The muscularis and the layers beneath it were, however, apparently normal. The gastric mucosa healed with little or no inflammation when sildenafil citrate, low dose heparin, ghrelin, NUCB2/Nesfatin‐1, obestatin, Neuropeptide Y were administered. Significance: Overall the data indicate that low dose heparin, and especially sildenafil citrate and neuropeptides, can be used clinically as an alternative approach in the treatment of the gastric ulcer. HIGHLIGHTSSildenafil citrate is the most promising agent in the treatment of gastric (peptic) ulcer.Neuropeptides can be important among the options for the treatment of gastric ulcers.Although heparin has the potential to treat the gastric ulcer, it is the weakest option.Nesfatin‐1, Obestatin and Neuropeptide Y decrease in the circulation and the gastric tissue when ulcers are present.

Immunohistochemical and quantitative analysis of ghrelin in Syzygium aromaticum

Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor, has been identified in mammals, fish, amphibians, birds, reptiles and some plants. The present investigation was designed to determine whether ghrelin is present in the appetite‐stimulating plants Syzygium aromaticum and Salvadora persica, using IHC (immunohistochemistry) to indicate the location of the peptide and ELISA to measure the concentration. ELISA demonstrated that a ghrelin‐like substance was present at concentrations of 4070.75±664.67 and 75.25±24.49 pg/mg in the tissues of flower bud of S. aromaticum and branch of S. persica, respectively. The concentration of ghrelin in human salivary gland tissue was 436.00±95.83 pg/mg. Ghrelin was predominantly localized to the T (trachea) and PCs (parenchyma cells) in the flower bud of S. aromaticum. However, no ghrelin immunoreactivity was observed in the PC or T of the branch of S. persica. The evolutionary role of this peptide hormone in plants and animals suggests that they have evolved in a more similar way than previously thought.