Effects of Sleeve Gastrectomy on Blood Pressure and the Renal Renin-Angiotensin System in Rats with Diet-Induced Obesity.

Objective: Sleeve gastrectomy (SG) has been reported to decrease blood pressure (BP), although the reason has not been revealed. The present study aimed to establish the reason why SG decreases BP.

Methods: Male Sprague-Dawley rats were subjected to surgical (sham operation or SG) and dietary interventions (fed a normal diet or high-fat diet ad libitum or fed by pair-feeding [PF]).

Glucagon-like peptide-1 reduces pancreatic β-cell mass through hypothalamic neural pathways in high-fat diet-induced obese rats.

We examined whether glucagon-like peptide-1 (GLP-1) affects β-cell mass and proliferation through neural pathways, from hepatic afferent nerves to pancreatic efferent nerves via the central nervous system, in high-fat diet (HFD)-induced obese rats. The effects of chronic administration of GLP-1 (7-36) and liraglutide, a GLP-1 receptor agonist, on pancreatic morphological alterations, c-fos expression and brain-derived neurotrophic factor (BDNF) content in the hypothalamus, and glucose metabolism were investigated in HFD-induced obese rats that underwent hepatic afferent vagotomy (VgX) and/or pancreatic efferent sympathectomy (SpX). Chronic GLP-1 (7-36) administration to HFD-induced obese rats elevated c-fos expression and BDNF content in the hypothalamus, followed by a reduction in pancreatic β-cell hyperplasia and insulin content, thus resulting in improved glucose tolerance.

Pore alterations of the endothelial lining of rat fenestrated intestinal capillaries exposed to acute stress.

Stress-induced inflammatory responses in the portal system are characterized by elevations in serum concentrations of interleukin-6 (IL-6) and endotoxins such as lipopolysaccharides (LPS). LPS translocation from the intestinal to the capillary lumen occurs via LPS endocytosis by the capillary endothelium. Because the capillary endothelium of the small intestinal submucosa is fenestrated, we determined the role of pore modifications within the fenestrated endothelium in relaying inflammatory stress responses in the portal vein.

Distribution of histaminergic neuronal cluster in the rat and mouse hypothalamus.

Histidine decarboxylase (HDC) catalyzes the biosynthesis of histamine from L-histidine and is expressed throughout the mammalian nervous system by histaminergic neurons. Histaminergic neurons arise in the posterior mesencephalon during the early embryonic period and gradually develop into two histaminergic substreams around the lateral area of the posterior hypothalamus and the more anterior peri-cerebral aqueduct area before finally forming an adult-like pattern comprising five neuronal clusters, E1, E2, E3, E4, and E5, at the postnatal stage. This distribution of histaminergic neuronal clusters in the rat hypothalamus appears to be a consequence of neuronal development and reflects the functional differentiation within each neuronal cluster.

A clinical approach to brown adipose tissue in the para-aortic area of the human thorax.

Background: Human thoracic brown adipose tissue (BAT), composed of several subdivisions, is a well-known target organ of many clinical studies; however, the functional contribution of each part of human thoracic BAT remains unknown. The present study analyzed the significance of each part of human thoracic BAT in the association between regional distribution, cellularity, and factors involved in the functional regulation of thoracic BAT.

Methods: We analyzed 1550 healthy adults who underwent medical check-ups by positron-emission tomography and computed tomography (PET-CT) imaging, 8 cadavers, and 78 autopsy cases in an observational study.

Effects of hydrophilic statins on renal tubular lipid accumulation in diet-induced obese mice.

Animal models of obesity show that lipid deposits can injure the kidneys,and there is evidence for the role of lipids in the development of chronic renal dis-ease (CKD). Statins exhibit a lipid-lowering effect that acts on both total cholesterol and triglyceride (TG) levels and pleiotropic effects including their ability to reduce inflammation and fibrosis. The purpose of the present study was to confirm whether obesity induced by a high-fat diet (HFD, 60% fat) promotes lipid accumulation in the tubulointerstitial and/or glomerular areas in the kidney, and whether treatment of several statins, pravastatin (30 mg/kg, p.

Effects of a nonnutritive sweetener on body adiposity and energy metabolism in mice with diet-induced obesity.

Objective: Nonnutritive sweeteners (NNSs) have been studied in terms of their potential roles in type 2 diabetes, obesity, and related metabolic disorders. Several studies have suggested that NNSs have several specific effects on metabolism such as reduced postprandial hyperglycemia and insulin resistance. However, the detailed effects of NNSs on body adiposity and energy metabolism have not been fully elucidated.

The dipeptidyl peptidase-4 inhibitor des-fluoro-sitagliptin regulates brown adipose tissue uncoupling protein levels in mice with diet-induced obesity.

Objective: Dipeptidyl peptidase (DPP)-4 is responsible for the degradation of several peptides that contain an alanine or proline at the penultimate position or position P1. DPP-4 inhibitors (DPP-4is) have protective effects against type-2 diabetes and several metabolic disorders.

Methods: In the present study, we examined the effects of des-fluoro-sitagliptin (DFS), a DDP-4i, on body adiposity and levels of peroxisome proliferator-activated receptor (PPAR)-α, PPAR-γ coactivator-1 (PGC-1), and uncoupling proteins (UCPs) in mice with diet-induced obesity.

Spleen-derived interleukin-10 downregulates the severity of high-fat diet-induced non-alcoholic fatty pancreas disease.

Obesity is associated with systemic low-grade inflammation and is a risk factor for non-alcoholic fatty pancreas disease (NAFPD), but the molecular mechanisms of these associations are not clear. Interleukin (IL)-10, a potent anti-inflammatory cytokine, is released during acute pancreatitis and is known to limit inflammatory responses by downregulating the release of proinflammatory mediators. The origin of IL-10 that suppresses pancreatitis has not been investigated.

Obesity-related chronic kidney disease is associated with spleen-derived IL-10.

Background: Obesity is associated with systemic low-grade inflammation and is a risk factor for chronic kidney disease (CKD), but the molecular mechanism remains uncertain. We noticed spleen-derived interleukin (IL)-10 because it is observed that obesity reduces several cytokines in the spleen.

Methods: We examined whether spleen-derived IL-10 regulates CKD caused by a high-fat diet (HF)-induced obesity as follows: (i) male mice were fed with HF (60% fat) during 8 weeks and IL-10 induction from the spleen was examined, (ii) glomerular hypertrophy, fibrosis, inflammatory responses in the kidney and systolic blood pressure (SBP) were evaluated in splenectomy (SPX)-treated mice fed HF, (iii) exogenous IL-10 was systemically administered to HF-induced obese mice and the alteration of obesity-induced pathogenesis caused by IL-10 treatment was assessed.

Cilnidipine regulates glucose metabolism and levels of high-molecular adiponectin in diet-induced obese mice.

The aim of the present study is to examine the effects of the antihypertensive drug cilnidipine on glucose metabolism and adipocytokines, including adiponectin, in diet-induced obese (DIO) mice. The effects of cilnidipine on insulin sensitivity and the levels of adiponectin in DIO mice were examined after the mice had been treated with cilnidipine dissolved in water at a dose of 0.2 g l(-1) for 14 days.

A novel anti-inflammatory role for spleen-derived interleukin-10 in obesity-induced inflammation in white adipose tissue and liver.

Obesity is associated with systemic low-grade inflammation and obesity-related metabolic disorders. Considering that obesity decreases the expression of proinflammatory cytokines in the spleen, we assessed the role of interleukin (IL)-10, an anti-inflammatory cytokine produced by the spleen, in the pathogenesis of obesity. Changes in obesity-related pathogenesis, including inflammatory responses in multiple organs, were assessed after systemic administration of exogenous IL-10 to splenectomy (SPX)-treated obese wild-type and IL-10 knockout (IL-10KO) mice.

Intracerebroventricular administration of urotensin II regulates food intake and sympathetic nerve activity in brown adipose tissue.

To clarify the functional roles of urotensin II in regulating energy balance, we investigated the effects of a central infusion of urotensin II on food intake, uncoupling protein (UCP) 1 mRNA expression, temperature, and sympathetic nervous system activity in brown adipose tissue (BAT), a site that regulates energy expenditure in rodents. A bolus central infusion of urotensin II at a dose of 1 nmol/rat into the third cerebral ventricle decreased food intake (p<0.05).

A novel anti-inflammatory role for spleen-derived interleukin-10 in obesity-induced hypothalamic inflammation.

Obesity can be associated with systemic low-grade inflammation that contributes to obesity-related metabolic disorders. Recent studies raise the possibility that hypothalamic inflammation contributes to the pathogenesis of diet-induced obesity (DIO), while another study reported that obesity decreases the expression of pro-inflammatory cytokines in spleen. The following study examines the hypothesis that obesity suppresses the splenic synthesis of the anti-inflammatory cytokine, interleukin (IL)-10, thereby resulting in chronic hypothalamic inflammation.

Intraportal administration of DPP-IV inhibitor regulates insulin secretion and food intake mediated by the hepatic vagal afferent nerve in rats.

Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion and suppresses food intake. Recent studies indicate that the hepatic vagal afferent nerve is involved in this response. Dipeptidyl peptidase-IV (DPP-IV) inhibitor extends the half-life of endogenous GLP-1 by preventing its degradation.

Hypothalamic neuronal histamine signaling in the estrogen deficiency-induced obesity.

Menopause is one of the triggers that induce obesity. Estradiol (E2), corticotropin-releasing hormone (CRH), and hypothalamic neuronal histamine are anorexigenic substances within the hypothalamus. This study examined the interactions among E2, CRH, and histamine during the regulation of feeding behavior and obesity in rodents.

Regional distribution and the dynamics of n-decanoyl ghrelin, another acyl-form of ghrelin, upon fasting in rodents.

n-Decanoyl ghrelin (D-ghrelin), a member of ghrelin-derived peptides, is found in plasma and the stomach; however, there have so far been no studies describing its dynamics. A D-ghrelin-specific radioimmunoassay was established to examine the tissue distribution and the kinetics of D-ghrelin in mice. The effect of D-ghrelin on food intake was also examined and compared to n-octanoyl ghrelin (O-ghrelin).

Acute central administration of immepip, a histamine H3 receptor agonist, suppresses hypothalamic histamine release and elicits feeding behavior in rats.

Histamine suppresses feeding behavior via histamine H1 receptors in the hypothalamus. This study was performed to examine whether the acute reduction of histamine release in the hypothalamus caused by immepip, a histamine H3 agonist, modulates the feeding behavior of rats. Rats had a catheter implanted in the third cerebral ventricle (i3v) and were given central injections of phosphate-buffered-saline or immepip (100-300 pmol/rat).

Retinol binding protein 4 concentrations are influenced by renal function in patients with type 2 diabetes mellitus.

Retinol binding protein 4 (RBP-4), a newly discovered adipocytokine, has been involved in glucose and lipid metabolism. We assess the impacts of renal function on plasma RBP-4 levels in patients with type 2 diabetes mellitus with a wide range of nephropathy. Plasma RBP-4 levels were measured using the enzyme immunoassay method in 38 type 2 diabetes mellitus patients with nephropathy and were compared with those in 20 patients with normoalbuminuria.