Grape Polyphenols May Prevent High-Fat Diet-Induced Dampening of the Hypothalamic-Pituitary-Adrenal Axis in Male Mice.

Context : Chronic high-fat diet (HFD) consumption causes obesity associated with retention of bile acids (BAs) that suppress important regulatory axes, such as the hypothalamic-pituitary-adrenal axis (HPAA). HFD impairs nutrient sensing and energy balance due to a dampening of the HPAA and reduced production and peripheral metabolism of corticosterone (CORT).

Objective: We assessed whether proanthocyanidin-rich grape polyphenol (GP) extract can prevent HFD-induced energy imbalance and HPAA dysregulation.

Proanthocyanidin B2 derived metabolites may be ligands for bile acid receptors S1PR2, PXR and CAR: an approach.

Bile acids (BAs) act as signaling molecules their interactions with various nuclear (FXR, VDR, PXR and CAR) and G-protein coupled (TGR5, M3R, S1PR2) BA receptors. Stimulation of these BA receptors influences several processes, including inflammatory responses and glucose and xenobiotic metabolism. BA profiles and BA receptor activity are deregulated in cardiometabolic diseases; however, dietary polyphenols were shown to alter BA profile and signaling in association with improved metabolic phenotypes.

Bile acid metabolism and signaling: Emerging pharmacological targets of dietary polyphenols.

Beyond their role as emulsifiers of lipophilic compounds, bile acids (BAs) are signaling endocrine molecules that show differential affinity and specificity for a variety of canonical and non-canonical BA receptors. Primary BAs (PBAs) are synthesized in the liver while secondary BAs (SBAs) are gut microbial metabolites of PBA species. PBAs and SBAs signal to BA receptors that regulate downstream pathways of inflammation and energy metabolism.

Saturated Fatty Acids and Omega-3 Polyunsaturated Fatty Acids Improve Metabolic Parameters in Ovariectomized Female Mice.

In menopausal and postmenopausal women, the risk for obesity, cardiovascular disease, osteoporosis, and gut dysbiosis are elevated by the depletion of 17β-estradiol. A diet that is high in omega-6 polyunsaturated fatty acids (PUFAs), particularly linoleic acid (LA), and low in saturated fatty acids (SFAs) found in coconut oil and omega-3 PUFAs may worsen symptoms of estrogen deficiency. To investigate this hypothesis, ovariectomized C57BL/6J and transgenic fat-1 mice, which lower endogenous omega-6 polyunsaturated fatty acids, were treated with either a vehicle or estradiol benzoate (EB) and fed a high-fat diet with a high or low PUFA:SFA ratio for ~15 weeks.

Impact of grape polyphenols on and the gut barrier.

A healthy gastrointestinal tract functions as a highly selective barrier, allowing the absorption of nutrients and metabolites while preventing gut bacteria and other xenobiotic compounds from entering host circulation and tissues. The intestinal epithelium and intestinal mucus provide a physical first line of defense against resident microbes, pathogens and xenotoxic compounds. Prior studies have indicated that the gut microbe , a mucin-metabolizer, can stimulate intestinal mucin thickness to improve gut barrier integrity.

Cannabidiol Decreases Intestinal Inflammation in the Ovariectomized Murine Model of Postmenopause.

Cannabidiol (CBD) (25 mg/kg peroral) treatment was shown to improve metabolic outcomes in ovariectomized (OVX) mice deficient in 17β-estradiol (E2). Herein, CBD effects on intestinal and hepatic bile acids (BAs) and inflammation were investigated. Following RNA sequencing of colon tissues from vehicle (VEH)- or CBD-treated sham surgery (SS) or OVX mice ( = 4 per group), differentially expressed genes (DEGs) were sorted in ShinyGO.

Coconut Oil Saturated Fatty Acids Improved Energy Homeostasis but not Blood Pressure or Cognition in VCD-Treated Female Mice.

Obesity, cardiometabolic disease, cognitive decline, and osteoporosis are symptoms of postmenopause, which can be modeled using 4-vinylcyclohexene diepoxide (VCD)-treated mice to induce ovarian failure and estrogen deficiency combined with high-fat diet (HFD) feeding. The trend of replacing saturated fatty acids (SFAs), for example coconut oil, with seed oils that are high in polyunsaturated fatty acids, specifically linoleic acid (LA), may induce inflammation and gut dysbiosis, and worsen symptoms of estrogen deficiency. To investigate this hypothesis, vehicle (Veh)- or VCD-treated C57BL/6J mice were fed a HFD (45% kcal fat) with a high LA:SFA ratio (22.

Corrigendum: Cannabidiol-treated ovariectomized mice show improved glucose, energy, and bone metabolism with a bloom in .

[This corrects the article DOI: 10.3389/fphar.2022.

Cannabidiol-Treated Ovariectomized Mice Show Improved Glucose, Energy, and Bone Metabolism With a Bloom in .

Loss of ovarian 17β-estradiol (E2) in postmenopause is associated with gut dysbiosis, inflammation, and increased risk of cardiometabolic disease and osteoporosis. The risk-benefit profile of hormone replacement therapy is not favorable in postmenopausal women therefore better treatment options are needed. Cannabidiol (CBD), a non-psychotropic phytocannabinoid extracted from hemp, has shown pharmacological activities suggesting it has therapeutic value for postmenopause, which can be modeled in ovariectomized (OVX) mice.

Grape Polyphenols Attenuate Diet-Induced Obesity and Hepatic Steatosis in Mice in Association With Reduced Butyrate and Increased Markers of Intestinal Carbohydrate Oxidation.

A Western Diet (WD) low in fiber but high in fats and sugars contributes to obesity and non-alcoholic fatty liver disease (NAFLD). Supplementation with grape polyphenols (GPs) rich in B-type proanthocyanidins (PACs) can attenuate symptoms of cardiometabolic disease and alter the gut microbiota and its metabolites. We hypothesized that GP-mediated metabolic improvements would correlate with altered microbial metabolites such as short chain fatty acids (SCFAs).

Polyphenol-induced improvements in glucose metabolism are associated with bile acid signaling to intestinal farnesoid X receptor.

Introduction: Bile acid (BA) biotransformation by gut bacteria impacts BA profile and signaling to nuclear receptors, such as the farnesoid X receptor (FXR) regulating glucose metabolism. Altered BA-FXR signaling was therefore investigated as a potential mechanism linking polyphenol-induced gut bacterial changes and improved glucose metabolism.

Research Design And Methods: Diabetic were fed low-fat diet (LFD) or LFD supplemented with a proanthocyanidin-rich extract of grape polyphenols (LFD-GP) for 4 weeks.

Grape proanthocyanidin-induced intestinal bloom of Akkermansia muciniphila is dependent on its baseline abundance and precedes activation of host genes related to metabolic health.

We previously showed that C57BL/6J mice fed high-fat diet (HFD) supplemented with 1% grape polyphenols (GP) for 12 weeks developed a bloom of Akkermansia muciniphila with attenuated metabolic syndrome symptoms. Here we investigated early timing of GP-induced effects and the responsible class of grape polyphenols. Mice were fed HFD, low-fat diet (LFD) or formulations supplemented with GP (HFD-GP, LFD-GP) for 14 days.

Transgenic overexpression of mitofilin attenuates diabetes mellitus-associated cardiac and mitochondria dysfunction.

Mitofilin, also known as heart muscle protein, is an inner mitochondrial membrane structural protein that plays a central role in maintaining cristae morphology and structure. It is a critical component of the mitochondrial contact site and cristae organizing system (MICOS) complex which is important for mitochondrial architecture and cristae morphology. Our laboratory has previously reported alterations in mitochondrial morphology and proteomic make-up during type 1 diabetes mellitus, with mitofilin being significantly down-regulated in interfibrillar mitochondria (IFM).

Functional deficiencies of subsarcolemmal mitochondria in the type 2 diabetic human heart.

The mitochondrion has been implicated in the development of diabetic cardiomyopathy. Examination of cardiac mitochondria is complicated by the existence of spatially distinct subpopulations including subsarcolemmal (SSM) and interfibrillar (IFM). Dysfunction to cardiac SSM has been reported in murine models of type 2 diabetes mellitus; however, subpopulation-based mitochondrial analyses have not been explored in type 2 diabetic human heart.

Effects of bicalutamide and leuprolide on prostate-specific antigen (PSA), acid phosphatase (ACP) and prostatic acid phosphatase (PAP) in men with benign prostatic hyperplasia (BPH).

The effects of the nonsteroidal antiandrogen bicalutamide (Casodex(TM)) and the luteinizing hormone releasing hormone agonist leuprolide depot (Procren Depot(TM), Lupron Depot(TM)) on serum prostate-specific antigen (PSA), acid phosphatase (ACP), and prostatic acid phosphatase (PAP) in patients with benign prostatic hyperplasia (BPH) were determined. Thirty patients with BPH were randomised to receive bicalutamide 50 mg orally once daily or a placebo for 24 weeks, followed by 24 weeks of follow-up (bicalutamide study). In another study 55 men were randomised between 3.

No randomised trial of prostate-cancer screening in Norway.

The Norwegian Urological Cancer Group (NUCG) decided against participating in the European Randomised Study on Screening for Prostate Cancer, to which they had planned to contribute data from a population of 75 000 men aged between 50 and 65. The plan was abandonned for three main reasons: Norwegian doubts about the statistical power of the trial, the possible ethical implications of screening a large number of men with no symptoms, and the belief that the trial would not produce clinically important results. In this review, the NUCG's reasons for not participating in the trial are discussed in full.

The effect of bicalutamide on prostate histology.

Background: Nonsteroidal antiandrogens are commonly used in the treatment of prostate cancer, but more clinical and laboratory studies on patients with benign as well as malignant prostate diseases are required to define their exact role.

Methods: Light microscopic examination of perineal prostate biopsies of 21 men with BPH was performed pretreatment, after 24 weeks of therapy with 50 mg bicalutamide (Casodex) or placebo and 24 weeks after end of treatment. We assessed whether it was possible to distinguish between patients having received bicalutamide or placebo based on a general histological examination.

[Treatment of renal carcinoma with distant metastases].

Background: There is no effective standard therapy for patients with distant metastases from renal cell carcinoma. Physicians should, however, know about the different treatment options and their efficacy in order to adequately inform and treat their patients.

Material And Methods: Current relevant literature and experience at the Norwegian Radium Hospital are reviewed with emphasis on systemic therapy.

Prognostic factors in patients with metastatic (stage D2) prostate cancer: experience from the Scandinavian Prostatic Cancer Group Study-2.

Purpose: Nuclear texture reflects the overall structures of the chromatin organization. We recently reported the principles and prognostic importance of image analysis of nuclei from metastatic prostate cancer. Immunohistochemical up regulation of the adhesion molecule sialyl Lewis(x) is also reported to be a prognostic parameter.

[Urosepsis].

Septicemia as a result of urinary infection is a serious condition, almost always caused by gram-negative bacteria. The bacterial toxins have a profound influence on haemostasis, microcirculation, and cardiac anf respiratory function. This article contains a brief review of aetiology, pathogenesis, pathophysiology, diagnostic work-up and treatment of this life-threatening condition.

Treatment of benign prostatic hyperplasia. A pharmacoeconomic perspective.

Men with moderate symptoms of benign prostatic hyperplasia (BPH) are the best candidates for medical treatment, while surgery is usually indicated for patients with severe symptoms. Men with mild symptoms do not usually need treatment, but they might be re-evaluated annually if desirable. Finasteride, which produces selective hormonal deprivation, is now established as a well tolerated drug for the long term medical therapy of BPH.

[Maximal androgen blockade in metastatic prostatic carcinoma].

In Norway the standard treatment for metastatic prostatic cancer has been surgical or medical castration. Only recently have antiandrogens been approved for treatment of advanced cancer of the prostate. The authors examine the principles for total or maximal androgen blockade and discuss American and European studies that indicate an improvement in survival as a result of maximal androgen blockade therapy in patients with low volume disease and good performance.