scholarly journals Caloric restriction modulates the monoaminergic system and metabolic hormones in aged rats

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marta Portero-Tresserra ◽  
D. Rojic-Becker ◽  
C. Vega-Carbajal ◽  
G. Guillazo-Blanch ◽  
A. Vale-Martínez ◽  
...  
Keyword(s):  
Caloric Restriction ◽  
High Performance ◽  
Dietary Intervention ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Occipital Cortex ◽  
Brain Regions ◽  
Metabolic Parameters ◽  
Negative Effects ◽  
Brain Monoamine

Abstract Caloric restriction (CR) can attenuate the general loss of health observed during aging, being one of the mechanisms involved the reduction of hormonal alteration, such as insulin and leptin. This change could also prevent age-specific fluctuations in brain monoamines, although few studies have addressed the effects of CR on peripheral hormones and central neurotransmitters exhaustively. Therefore, the variations in brain monoamine levels and some peripheral hormones were assessed here in adult 4-month old and 24-month old male Wistar rats fed ad libitum (AL) or maintained on a 30% CR diet from four months of age. Noradrenaline (NA), dopamine (DA), serotonin (5-HT) and its metabolites were measured by high-performance liquid chromatography with electrochemical detection (HPLC-ED) in nine brain regions: cerebellum, pons, midbrain, hypothalamus, thalamus, hippocampus, striatum, frontal cortex, and occipital cortex. In addition, the blood plasma levels of hormones like corticosterone, insulin and leptin were also evaluated, as were insulin-like growth factor 1 and other basal metabolic parameters using enzyme-linked immunosorbent assays (ELISAs): cholesterol, glucose, triglycerides, albumin, low-density lipoprotein, calcium and high-density lipoprotein (HDLc). CR was seen to increase the NA levels that are altered by aging in specific brain regions like the striatum, thalamus, cerebellum and hypothalamus, and the DA levels in the striatum, as well as modifying the 5-HT levels in the striatum, hypothalamus, pons and hippocampus. Moreover, the insulin, leptin, calcium and HDLc levels in the blood were restored in old animals maintained on a CR diet. These results suggest that a dietary intervention like CR may have beneficial health effects, recovering some negative effects on peripheral hormones, metabolic parameters and brain monoamine concentrations.

scholarly journals Neurotoxic astrocytic glypican-4 drives APOE4-dependent tau pathology

2021 ◽  
Author(s):  
Sivaprakasam Ramamoorthy ◽  
Kirill Gorbachev ◽  
Ana Pereira
Keyword(s):  
Late Onset ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Brain Regions ◽  
Tau Proteins ◽  
Tau Pathology ◽  
Density Lipoprotein Receptor ◽  
Apoe Receptor ◽  
The Brain

Apolipoprotein E4 (APOE4) is the crucial genetic risk factor of late-onset Alzheimer disease (AD). Aggregation of tau proteins into insoluble filaments and their spreading across the brain regions are major drivers of neurodegeneration in tauopathies, including in AD. However, the exact mechanisms through which APOE4 induces tau pathology remains unknown. Here, we report that the astrocyte-secreted protein glypican-4 (GPC-4), a novel binding partner of APOE4, drives tau pathology. GPC-4 preferentially interacts with APOE4 in comparison to other APOE isoforms and post-mortem APOE4-carrying AD brains highly express GPC-4 in neurotoxic astrocytes. The astrocyte-secreted GPC-4 induced both tau accumulation and propagation in vitro. CRISPR/dCas9 mediated activation of GPC-4 in a tauopathy animal model robustly induced tau pathology. Further, APOE4-induced tau pathology was greatly diminished in the absence of GPC-4. We found that GPC-4 promoted the stabilization of the APOE receptor low-density lipoprotein receptor-related protein 1 (LRP1) on the cellular surface, which effectively facilitates endocytosis of tau protein. Together, our data comprehensively demonstrate that one of the key APOE4-induced tau pathologies is directly mediated by GPC-4.

scholarly journals The Effect of Bariatric Surgery on Weight Loss and Metabolic Changes in Adults with Obesity

2020 ◽  
Vol 17 (15) ◽  
pp. 5342
Author(s):  
Stanisław Głuszek ◽  
Arkadiusz Bociek ◽  
Edyta Suliga ◽  
Jarosław Matykiewicz ◽  
Magdalena Kołomańska ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Weight Loss ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Metabolic Changes ◽  
Metabolic Parameters ◽  
Lipoprotein Cholesterol ◽  
Excess Body Weight ◽  
Eligibility Criteria

Methods of treating obesity, such as changes in lifestyle, physical activity, restrictive diets, and psychotherapy, are not sufficient. Currently, it is considered that in the case of patients who meet the eligibility criteria for surgery, the treatment of choice should be bariatric surgery. The aim of this study was to assess the weight loss and metabolic changes in a group of adults with obesity undergoing bariatric surgery. The study involved 163 patients whose body mass index (BMI) exceeded 40 or 35 kg/m2, concurrent with at least one metabolic sequelae. In 120 of the cases (74%), sleeve gastrectomy was used; in 35 (21%), gastric banding was used; and in 8 (5%), laparoscopic Roux-en-Y gastric bypass was used. Metabolic parameters such as total cholesterol, LDL-cholesterol (low-density lipoprotein cholesterol), HDL-cholesterol (high-density lipoprotein cholesterol), triglycerides, and glucose were measured preoperatively and postoperatively, as well as the creatinine, creatine kinase (CK-MB), and leptin activity. In patients undergoing bariatric surgery, a significant decrease in excess weight (p < 0.001) was observed at all the analyzed time points, compared to the pre-surgery value. Weight loss after surgery was associated with a significant improvement in glycemia (109.6 ± 48.0 vs. 86.6 ± 7.9 mg/dL >24 months after surgery; p = 0.003), triglycerides (156.9 ± 79.6 vs. 112.7 ± 44.3 mg/dL >24 months after surgery; p = 0.043) and leptin (197.50 ± 257.3 vs. 75.98 ± 117.7 pg/mL 12 months after surgery; p = 0.0116) concentration. The results of the research confirm the thesis on the effectiveness of bariatric surgery in reducing excess body weight and improving metabolic parameters in patients with extreme obesity.

Correlation between vaspin and PANSS scores in schizophrenia patients with obesity

2020 ◽  
Vol 55 (4) ◽  
pp. 264-280
Author(s):  
Hülya Ertekin ◽  
Sema Uysal ◽  
Memduha Aydın ◽  
Bilge İlhan ◽  
Yusuf Haydar Ertekin
Keyword(s):  
Metabolic Syndrome ◽  
Plasma Levels ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Metabolic Parameters ◽  
Healthy Controls ◽  
Positive Correlation ◽  
Syndrome Scale ◽  
Positive Correlations ◽  
Negative Syndrome

Objective Metabolic abnormalities such as diabetes, dyslipidemia, abdominal obesity, metabolic syndrome, and abnormal levels of plasma adipokines have been observed in patients with schizophrenia. This study aimed to investigate the differences and correlations of plasma vaspin levels with metabolic parameters in patients with schizophrenia and to compare with healthy controls. Method We measured plasma levels of vaspin and metabolic parameters of 100 patients with schizophrenia and 95 healthy controls. Patients with schizophrenia were evaluated with the Positive and Negative Syndrome Scale (PANSS) and The Global Assessment of Functioning. Results Mean levels of body mass index, waist circumference, triglyceride, and low-density lipoprotein cholesterol of the patients were statistically higher than those of the healthy controls (p = 0.002, p < 0.001, p = 0.03, and p = 0.002, respectively). Plasma levels of vaspin were 0.96 ± 0.73 ng/ml in patients with schizophrenia and 0.29 ± 0.15 ng/ml in the healthy controls (p < 0.001). Plasma vaspin levels were statistically higher in patients with schizophrenia than healthy controls both in groups with and without metabolic syndrome and obesity (p < 0.001). Plasma vaspin levels showed a positive correlation with triglyceride in patients with schizophrenia (r = 0.26, p = 0.007). There were positive correlations between vaspin and PANSS scores in schizophrenia patients with obesity (PANSS Positive: r = 0.42, p = 0.01; PANSS Negative: r = 0.42, p = 0.01; PANSS General: r = 0.43, p = 0.01; PANSS Total: r = 0.47, p = 0.006). Conclusions Our study showed a significant relationship and positive correlation between vaspin and PANSS scores in schizophrenia patients with obesity. Vaspin may play an important role in the metabolic processes of patients with schizophrenia.

scholarly journals The Effect of Kelulut Honey on Fasting Blood Glucose and Metabolic Parameters in Patients with Impaired Fasting Glucose

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Mohd Radzniwan Rashid ◽  
Khairun Nain Nor Aripin ◽  
Fathima Begum Syed Mohideen ◽  
Nizam Baharom ◽  
Khairani Omar ◽  
...  
Keyword(s):  
Impaired Fasting Glucose ◽  
Fasting Glucose ◽  
Low Density Lipoprotein ◽  
Fasting Blood Glucose ◽  
Daily Intake ◽  
Density Lipoprotein ◽  
Metabolic Parameters ◽  
Control Group ◽  
Significant Difference ◽  
Group Control Group

Background. Impaired fasting glucose (IFG) poses a higher risk of diabetes. Honey has been reported to improve metabolic abnormalities including lowering hyperglycemia. This study is sought at determining the effect of Malaysian Kelulut honey (KH) on fasting glucose levels and metabolic parameters in IFG patients. Methods. This quasi-experimental intervention study of 30-day duration was conducted among 60 adult patients with IFG. They were allocated into taking 30 g/day KH group (experimental group, n=30) and not taking KH group (control group, n=30). Body mass index (BMI), waist circumference, blood pressure (BP), fasting glucose, and lipid profile levels (total cholesterol, triglyceride, high-density lipoprotein, and low-density lipoprotein) were measured before and after treatment. Results. There was no significant difference in all measured variables at day 30 compared to day 1 within both groups. Similarly, all measured variables neither at day 1 nor at day 30 had shown a statistically significant difference between the groups. Conclusions. Daily intake of 30 g KH for 30 days resulted in insignificant effect on fasting glucose, fasting lipid profiles, and other metabolic parameters in patients with IFG. Further studies that employ longer study duration are needed to ascertain the finding.

scholarly journals An Untargeted Lipidomic Analysis Reveals Depletion of Several Phospholipid Classes in Patients with Familial Hypercholesterolemia on Treatment with Evolocumab

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1941
Author(s):  
Andrea Anesi ◽  
Alessandro Di Di Minno ◽  
Ilenia Calcaterra ◽  
Viviana Cavalca ◽  
Maria Tripaldella ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
High Performance ◽  
De Novo ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Unsaturation Index ◽  
Fatty Acyl ◽  
Phospholipid Classes

Rationale: Familial hypercholesterolemia (FH) is caused by mutations in genes involved in low-density lipoprotein cholesterol (LDL-C) metabolism, including those for pro-protein convertase subtilisin/kexin type 9 (PCSK-9). The effect of PCSK-9 inhibition on the plasma lipidome has been poorly explored. Objective: Using an ultra-high-performance liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry method, the plasma lipidome of FH subjects before and at different time intervals during treatment with the PCSK-9 inhibitor Evolocumab was explored. Methods and Results: In 25 FH subjects, heterozygotes or compound heterozygotes for different LDL receptor mutations, untargeted lipidomic revealed significant reductions in 26 lipid classes belonging to phosphatidylcholine (PC), sphingomyelin (SM), ceramide (CER), cholesteryl ester (CE), triacylglycerol (TG) and phosphatidylinositol (PI). Lipid changes were graded between baseline and 4- and 12-week treatment. At 12-week treatment, five polyunsaturated diacyl PC, accounting for 38.6 to 49.2% of total PC at baseline; two ether/vinyl ether forms; seven SM; five CER and glucosyl/galactosyl-ceramide (HEX-CER) were reduced, as was the unsaturation index of HEX-CER and lactosyl—CER (LAC-CER). Although non quantitative modifications were observed in phosphatidylethanolamine (PE) during treatment with Evolocumab, shorter and more saturated fatty acyl chains were documented. Conclusions: Depletion of several phospholipid classes occurs in plasma of FH patients during treatment with the PCSK-9 inhibitor Evolocumab. The mechanism underlying these changes likely involves the de novo synthesis of SM and CER through the activation of the key enzyme sphingomyelin synthase by oxidized LDL and argues for a multifaceted system leading to vascular improvement in users of PCSK-9 inhibitors.

scholarly journals A STUDY OF METABOLIC PARAMETERS IN NON DIABETIC PATIENTS WITH NON ALCOHOLIC FATTY LIVER DISEASE - IMPORTANCE OF DYSLIPIDEMIA

2019 ◽  
Vol 56 (3) ◽  
pp. 270-275 ◽  
Author(s):  
Gautam RAY ◽  
Trilochan AGARWALA
Keyword(s):  
Glucose Tolerance ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Normal Glucose Tolerance ◽  
Metabolic Parameters ◽  
Lipoprotein Cholesterol ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Normal Glucose ◽  
Alcoholic Fatty Liver Disease

ABSTRACT BACKGROUND: Metabolic risk factors of non alcoholic fatty liver disease (NAFLD) in non diabetic teetotallers who constitute a definite group are not well defined. OBJECTIVE: To identify the metabolic risk factors of NAFLD if any in non diabetic subjects who do not consume alcohol. METHODS: In a cross sectional study the effect of metabolic parameters (BMI, individual lipid levels, hemoglobinA1c (HbA1c), HOMA IR and the metabolic syndrome components) of 150 consecutive non diabetic teetotallers (90 with normal glucose tolerance and 60 prediabetics) on their NFS (quantifiable severity parameter of NAFLD) was studied by linear regression analysis. Similar study was done in the normal glucose tolerance and prediabetes groups separately. These parameters were then compared with those of 75 matched diabetic teetotallers with NAFLD. To analyse further the difference between normal glucose tolerance, prediabetic and overt diabetic groups, binary logistic regression of the factors was carried out taking prediabetes and diabetes as outcome variable. RESULTS: All the metabolic parameters were significantly higher in diabetics compared to non diabetics and in prediabetics compared to those with normal glucose tolerance except high-density lipoprotein cholesterol. Triglyceride, high-density lipoprotein cholesterol and BMI significantly predicted NFS in the overall (adjusted R2 68.7%, P=0.000) and normal glucose tolerance groups (adjusted R2 73.2%, P=0.000) whereas BMI, triglyceride, low-density lipoprotein cholesterol and HbA1c did in prediabetics (adjusted R2 89%, P=0.000). The metabolic syndrome was significantly associated with NFS in the overall and prediabetic groups. High triglyceride (odds ratio1.08), low-density lipoprotein cholesterol (odds ratio1.03) and HbA1c (odds ratio 11.54) were positively associated with prediabetes compared to normal glucose tolerance group. CONCLUSION: In nondiabetic teetotallers dyslipidemias are the prime contributors to the development of NAFLD.

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