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Obesity usually induces overactive bladder (OAB) associated with detrusor overactivity, which is related to increased contractility of the detrusor smooth muscle (DSM). Small-conductance Ca2+-activated K+ (SK) channels play a constitutive role in the regulation of DSM contractility. However, the role of SK channels in the DSM changes in obesity-related OAB is still unknown. Here, we tested the hypothesis that obesity-related OAB is associated with reduced expression and activity of SK channels in DSM and that SK channels activation is a potential treatment for OAB. Female Sprague–Dawley rats were fed a normal diet (ND) or a high-fat diet (HFD) and weighed after 12 weeks. Urodynamic studies, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and isometric tension recording were performed. Increased average body weights and urodynamically demonstrated OAB were observed in HFD rats. qRT-PCR experiments revealed a decrease in the mRNA expression level of SK channel in DSM tissue of the HFD rats. Isometric tension recordings indicated an attenuated relaxation effect of NS309 on the spontaneous phasic and electrical field stimulation-induced contractions that occurred via SK channel activation in HFD DSM strips. Reduced expression and activity of SK channels in the DSM contribute to obesity-related OAB, indicating that SK channels are a potential therapeutic target for OAB.

We aimed to clarify the key factor determining the effect of beta blocker attenuating high fat diet- induced obesity and bone loss. Six-week-old C57BL/6 male mice were assigned to groups reflecting different relative onset of obesity and beta blocker administration, different diet (control vs. high fat), and treatment (vehicle vs. beta blocker: propranolol). Mice in Group 1 were fed a control diet (CON) or high fat diet (HIGH) with vehicle or propranolol for 12 weeks. Mice in Group 2 were fed a CON or HIGH without pharmaceutical treatment for the first 12 weeks, followed by another 12 weeks of treatment with vehicle or propranolol. Mice in Group 3 were fed a CON without pharmaceutical treatment for the first 12 weeks, followed by stratification into diet-based subgroups and another 12 weeks of treatment with vehicle or propranolol. Propranolol attenuated the HIGH-induced increase in body weight/fat mass in Group 1 mice and in Group 3 mice, but not in Group 2 mice. Propranolol mitigated HIGH-induced reduction in femoral trabecular bone mineral density and bone architecture deterioration in Group 1 mice but not in Group 2 mice. HIGH feeding in Group 3 did not compromise skeletal integrity. Taken together, propranolol attenuates HIGH-induced body weight increases while weight gain is in progress but not once obesity has already been established. HIGH feeding during the growth period results in compromised bone mass/architecture; which can be attenuated by propranolol administration during the growth period, but not by propranolol administration after obesity has already been established.

Background Obesity has deleterious effects on the brain, and metabolic dysfunction may exacerbate the outcomes of seizures and brain injuries. However, it is unclear whether obesity affects excitotoxicity-induced neuronal cell death. The purpose of this study was to investigate the effects of a high-fat diet (HFD) on neuroinflammation and oxidative stress in the hippocampus of kainic acid (KA)-treated mice. Results Mice were fed with a HFD or normal diet for 8 weeks and then received a systemic injection of KA. HFD-fed mice showed hypercholesterolemia, insulin resistance, and hepatic steatosis. HFD-fed mice showed greater susceptibility to KA-induced seizures, an increased number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, neuroinflammation, and oxidative stress. Furthermore, we found that KA treatment increased HFD-induced calpain1, nuclear factor E2-related factor 2, and heme oxygenase-1 expression in the hippocampus. Conclusions These findings imply that complex mechanisms affected by obesity-induced systemic inflammation, neuroinflammation, ER stress, calcium overload, and oxidative stress may contribute to neuronal death after brain injury. Electronic supplementary material The online version of this article (doi:10.1186/s12868-015-0202-2) contains supplementary material, which is available to authorized users.

Several biologically active compounds are present in seaweeds that show a wide range of biological properties, such as antibiotic, anti-inflammatory, antioxidant, cytotoxic, antitumour and anti-obesity activities. The aim was to evaluate the anti-obesity effects of chronic treatment with Norwegian Ascophyllum nodosum phytocomplex in rats. We also investigated the effects of this phytocomplex on blood glucose and serum lipid levels, and α-amylase, lipase, alanine aminotransferase and aspartate aminotransferase activities. Five groups of male Sprague-Dawley rats were fed for 8 weeks with standard diet, highfat diet (HFD) or HFD plus three different doses of Norwegian A. nodosum phytocomplex (HFD Low, HFD Medium, HFD High). Feeding with HFD resulted in increased body weight and deposition of visceral and abdominal white adipose tissue. These effects were significantly reduced by supplementation with high doses of A. nodosum phytocomplex in the feed, which suggests a potent anti-obesity activity of this phytocomplex. Increased serum levels of triglycerides and α-amylase activity were observed in rats fed with HFD at sacrifice. These were inhibited in a dose-dependent manner by feeding with the added A. nodosum phytocomplex in HFD Medium and HFD High. Increased liver and kidney weights were also inhibited in a dose-dependent manner by added A. nodosum phytocomplex, with significant effects at the highest phytocomplex dose. Rats fed with HFD showed a changed, irregular, liver morphology, increased infiltration of inflammatory cells and increased intravascular spaces compared to controls. These effects were partially corrected by HFD High, which suggests potent anti-inflammatory activity of the A. nodosum phytocomplex.

Apolipoprotein A5 (ApoA5) is thought to function as an activator of LPL-mediated hydrolysis of triglyceride-rich lipoproteins and to facilitate endocytosis of lipid poor remnants. Mutations in ApoA5 have been described to be associated with hypertriglyceridemia in humans and mice. However, the low plasma concentration of ApoA5 compared to its high intracellular concentration suggests that this may not be the main role.