Role of adenosine in insulin-stimulated release of leptin from isolated white adipocytes of Wistar rats

High-fat diets (HFD) have been widely associated with an increased risk of metabolic disorders and overweight. However, a high intake of sources that are rich in monounsaturated fatty acids has been suggested as a dietary agent that is able to positively influence energy metabolism and vascular function. The main objective of this study was to analyze the role of dietary fats on hepatic peptidases activities and metabolic disorders. Three diets: standard (S), HFD supplemented with virgin olive oil (VOO), and HFD supplemented with butter plus cholesterol (Bch), were administered over six months to male Wistar rats. Plasma and liver samples were collected for clinical biochemistry and aminopeptidase activities (AP) analysis. The expression of inducible nitric oxide synthase (iNOS) was also determined by Western blot in liver samples. The diet supplement with VOO did not induce obesity, in contrast to the Bch group. Though the VOO diet increased the time that was needed to return to the basal levels of plasma glucose, the fasting insulin/glucose ratio and HOMA2-%B index (a homeostasis model index of insulin secretion and valuation of β-cell usefulness (% β-cell secretion)) were improved. An increase of hepatic membrane-bound dipeptidyl-peptidase 4 (DPP4) activity was found only in VOO rats, even if no differences in fasting plasma glucagon-like peptide 1 (GLP-1) were obtained. Both HFDs induced changes in hepatic pyroglutamyl-AP in the soluble fraction, but only the Bch diet increased the soluble tyrosyl-AP. Angiotensinase activities that are implicated in the metabolism of angiotensin II (AngII) to AngIV increased in the VOO diet, which was in agreement with the higher activity of insulin-regulated-AP (IRAP) in this group. Otherwise, the diet that was enriched with butter increased soluble gamma-glutamyl transferase (GGT) and Leucyl-AP, iNOS expression in the liver, and plasma NO. In summary, VOO increased the hepatic activity of AP that were related to glucose metabolism (DPP4, angiotensinases, and IRAP). However, the Bch diet increased activities that are implicated in the control of food intake (Tyrosine-AP), the index of hepatic damage (Leucine-AP and GGT), and the expression of hepatic iNOS and plasma NO. Taken together, these results support that the source of fat in the diet affects several peptidases activities in the liver, which could be related to alterations in feeding behavior and glucose metabolism.

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Irisin exerts dual effects on browning and adipogenesis of human white adipocytes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00094.2016 ◽

2016 ◽

Vol 311 (2) ◽

pp. E530-E541 ◽

Cited By ~ 64

Author(s):

Yuan Zhang ◽

Chao Xie ◽

Hai Wang ◽

Robin M. Foss ◽

Morgan Clare ◽

...

Keyword(s):

Adipose Tissue ◽

Uncoupling Protein ◽

Adipogenic Differentiation ◽

Mapk Signaling ◽

Cellular Energy ◽

Subcutaneous White Adipose Tissue ◽

Basal Expression ◽

White Adipocytes ◽

Ucp1 Expression

To better understand the role of irisin in humans, we examined the effects of irisin in human primary adipocytes and fresh human subcutaneous white adipose tissue (scWAT). Human primary adipocytes derived from 28 female donors' fresh scWAT were used to examine the effects of irisin on browning and mitochondrial respiration, and preadipocytes were used to examine the effects of irisin on adipogenesis and osteogenesis. Cultured fragments of scWAT and perirenal brown fat were used for investigating signal transduction pathways that mediate irisin's browning effect by Western blotting to detect phosphorylated forms of p38, ERK, and STAT3 as well as uncoupling protein 1 (UCP1). Individual responses to irisin in scWAT were correlated with basal expression levels of brown/beige genes. Irisin upregulated the expression of browning-associated genes and UCP1 protein in both cultured primary mature adipocytes and fresh adipose tissues. It also significantly increased thermogenesis at 5 nmol/l by elevating cellular energy metabolism (OCR and ECAR). Treating human scWAT with irisin increased UCP1 expression by activating the ERK and p38 MAPK signaling. Blocking either pathway with specific inhibitors abolished irisin-induced UCP1 upregulation. However, our results showed that UCP1 in human perirenal adipose tissue was insensitive to irisin. Basal levels of brown/beige and FNDC5 genes correlated positively with the browning response of scWAT to irisin. In addition, irisin significantly inhibited adipogenic differentiation but promoted osteogenic differentiation. We conclude that irisin promotes “browning” of mature white adipocytes by increasing cellular thermogenesis, whereas it inhibits adipogenesis and promotes osteogenesis during lineage-specific differentiation. Our findings provide a rationale for further exploring the therapeutic use of irisin in obesity and exercise-associated bone formation.

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A Possible Inflammatory Role of Twist1 in Human White Adipocytes

Diabetes ◽

10.2337/db09-0997 ◽

2009 ◽

Vol 59 (3) ◽

pp. 564-571 ◽

Cited By ~ 29

Author(s):

A. T. Pettersson ◽

J. Laurencikiene ◽

N. Mejhert ◽

E. Naslund ◽

A. Bouloumie ◽

...

Keyword(s):

White Adipocytes

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Ouabain- and central sodium-induced hypertension depend on the ventral anteroventral third ventricle region

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1999.276.1.h63 ◽

1999 ◽

Vol 276 (1) ◽

pp. H63-H70 ◽

Cited By ~ 8

Author(s):

Shereeni J. Veerasingham ◽

Frans H. H. Leenen

Keyword(s):

Hypertonic Saline ◽

Wistar Rats ◽

Third Ventricle ◽

Cardiovascular Responses ◽

Ibotenic Acid ◽

Air Jet ◽

Artificial Cerebrospinal Fluid ◽

Induced Hypertension ◽

Chronic Infusion

To examine the role of the ventral anteroventral third ventricle (vAV3V) in the hypertension induced by chronic subcutaneous ouabain and intracerebroventricular hypertonic saline, neurons in this area were destroyed by microinjection of an excitotoxin, ibotenic acid. Sham-operated or lesioned Wistar rats were administered ouabain (50 μg/day) or placebo for 3 wk from subcutaneously implanted controlled release pellets or artificial cerebrospinal fluid (CSF) or CSF containing 0.8 mol/l NaCl (5 μl/h) infused intracerebroventricularly for 2 wk. At the end of the experiment, mean arterial pressure (MAP) and heart rate at rest and in response to ganglionic blockade by intravenous hexamethonium (30 mg/kg) were assessed. In rats infused with hypertonic saline, responses to air jet stress were also assessed. Baseline MAP in sham-operated rats receiving intracerebroventricular hypertonic saline or subcutaneous ouabain was significantly higher than in control rats (115 ± 1 vs. 97 ± 3 and 121 ± 3 vs. 103 ± 3 mmHg, respectively). vAV3V lesions abolished the increase in MAP elicited by chronic infusion of hypertonic saline or administration of ouabain. Sham-operated rats treated with hypertonic saline or ouabain exhibited significantly enhanced decreases in MAP to hexamethonium, but lesioned rats did not. Rats infused with hypertonic saline demonstrated enhanced responses to air jet stress that were similar in sham-operated and lesioned rats. These results demonstrate that neurons in the vAV3V are essential for the hypertension induced by intracerebroventricular hypertonic saline and subcutaneous ouabain, possibly by increasing sympathetic tone. Cardiovascular responses to air jet stress appear not to be mediated by the vAV3V.

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Acetylcholine and muscarinic receptor function in cerebral cortex of diabetic young and old male Wistar rats and the role of muscarinic receptors in calcium release from pancreatic islets

Biogerontology ◽

10.1007/s10522-009-9237-z ◽

2009 ◽

Vol 11 (2) ◽

pp. 151-166 ◽

Cited By ~ 3

Author(s):

Balakrishnan Savitha ◽

Binoy Joseph ◽

T. Peeyush Kumar ◽

C. S. Paulose

Keyword(s):

Cerebral Cortex ◽

Pancreatic Islets ◽

Muscarinic Receptor ◽

Muscarinic Receptors ◽

Wistar Rats ◽

Calcium Release ◽

Receptor Function ◽

Male Wistar Rats

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Cardioprotective Properties of Opioid Receptor Agonists in Rats With Stress-Induced Cardiac Injury

Physiological Research ◽

10.33549/physiolres.933946 ◽

2019 ◽

pp. 375-384

Author(s):

E. PROKUDINA ◽

L MASLOV ◽

N. NARYZHNAYA ◽

S. TSIBULNIKOV ◽

Y. LISHMANOV ◽

...

Keyword(s):

Opioid Receptor ◽

Wistar Rats ◽

Immobilization Stress ◽

Cardiac Injury ◽

Endogenous Opioids ◽

Heart Injury ◽

Mr 2266 ◽

Opioid Receptor Agonists ◽

Stimulation Of

The objectives of this study were to investigate the role of endogenous opioids in the mediation of stress-induced cardiomyopathy (SIC), and to evaluate which opioid receptors regulate heart resistance to immobilization stress. Wistar rats were subjected to 24 h immobilization stress. Stress-induced heart injury was assessed by 99mTc-pyrophosphate accumulation in the heart. The opioid receptor (OR) antagonists (naltrexone, NxMB – naltrexone methyl bromide, MR 2266, ICI 174.864) and agonists (DALDA, DAMGO, DSLET, U-50,488) were administered intraperitoneally prior to immobilization and 12 h after the start of stress. In addition, the selective µ OR agonists PL017 and DAMGO were administered intracerebroventricularly prior to stress. Finally pretreatment with guanethidine was used. Naltrexone did not alter the cardiac 99mTc-PP accumulation in stressed rats. NxMB aggravated stress-induced cardiomyopathy (P=0.005) (SIC). The selective µ OR agonist DALDA, which does not cross the blood-brain barrier, completely prevented (P=0.006) SIC. The µ OR agonist DAMGO exhibited weaker effect than DALDA. The selective δ ligand (DSLET) and κ OR ligand (U-50,488) did not alter stress-induced 99mTc-pyrophosphate accumulation in the heart. Intracerebroventricular administration of the µ OR agonists aggravated SIC. Pretreatment with guanethidine abolished this effect (P=0.01). Guanethidine alone exhibited cardioprotective properties. A stimulation of central µ OR promotes an appearance of SIC. In contrast, stimulation of peripheral µ OR contributes to an increase in cardiac tolerance to stress.

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