Effects of lactogen resistance and GH deficiency on mouse metabolism: pancreatic hormones, adipocytokines, and expression of adiponectin and insulin receptors

We recently described a novel mouse model that combines resistance to lactogenic hormones with GH deficiency (GHD). The GHD/lactogen-resistant males develop obesity and insulin resistance with age. We hypothesized that altered production of pancreatic hormones and dysregulation of adipocytokine secretion and action contribute to the pathogenesis of their insulin resistance. Double-mutant males (age 12–16 months) had fasting hyperinsulinemia, hyperamylinemia, hyperleptinemia, and a decreased ratio of adiponectin to leptin. Adiponectin receptor 1 and 2 (AdipoR1 and R2) mRNA levels in liver and skeletal muscle were normal but hepatic insulin receptor mRNA was increased. Relative to double-mutant males, GHD males had lower levels of insulin, amylin, and leptin, higher levels of adiponectin, and higher expression of hepatic AdipoR1 and insulin receptor mRNAs. Lactogen-resistant mice had reduced hepatic adipoR2 mRNA. In response to stress the plasma concentrations of MCP-1 and IL-6 increased in double-mutant males but not GHD or lactogen-resistant males. Our findings suggest that the insulin resistance of GHD/lactogen-resistant males is accompanied by dysregulation of pancreatic hormone and adipocytokine secretion and receptor expression. Phenotypic differences between double-mutant and GHD males suggest that lactogens and GH exert differential but overlapping effects on fat deposition and adipocytokine secretion and action.     

Rutin attenuates metabolic changes, nonalcoholic steatohepatitis, and cardiovascular remodeling in high-carbohydrate, high-fat diet-fed rats

Metabolic syndrome (obesity, diabetes, and hypertension) increases hepatic and cardiovascular damage. This study investigated preventive or reversal responses to rutin in high-carbohydrate, high-fat diet-fed rats as a model of metabolic syndrome. Rats were divided into 6 groups: 2 groups were fed a corn starch-rich diet for 8 or 16 wk, 2 groups were fed a high-carbohydrate, high-fat diet for 8 or 16 wk, and 2 groups received rutin (1.6 g/kg diet) in either diet for the last 8 wk only of the 16-wk protocol. Metabolic changes and hepatic and cardiovascular structure and function were then evaluated in these rats. The corn starch-rich diet contained 68% carbohydrate (mainly cornstarch) and 0.7% fat, whereas the high-carbohydrate, high-fat diet contained 50% carbohydrate (mainly fructose) and 24% fat (mainly beef tallow) along with 25% fructose in drinking water (total 68% carbohydrate using mean food and water intakes). The high-carbohydrate, high-fat diet produced obesity, dyslipidemia, hypertension, impaired glucose tolerance, hepatic steatosis, infiltration of inflammatory cells in the liver and the heart, higher cardiac stiffness, endothelial dysfunction, and higher plasma markers of oxidative stress with lower expression of markers for oxidative stress and apoptosis in the liver. Rutin reversed or prevented metabolic changes such as abdominal fat pads and glucose tolerance, reversed or prevented changes in hepatic and cardiovascular structure and function, reversed oxidative stress and inflammation in the liver and heart, and normalized expression of liver markers. These results suggest a non-nutritive role for rutin to attenuate chronic changes in metabolic syndrome.     

Synthesis and antimicrobial activity of highly functionalised novel β-lactam grafted spiropyrrolidines and pyrrolizidines

A facile and one-pot synthesis of a series of novel spiropyrrolidines/pyrrolizidines with β-lactam substituent has been accomplished through 1,3-dipolar cycloaddition reaction of alkenyl esters derived from β-lactam aldehyde as dipolarophile with the dipole azomethine ylide derived from 1,2- and 1,3-diketones and secondary amino acids. The synthesized compounds were evaluated for antimicrobial activities and found to exhibit relatively good antibacterial activity at lower concentration against four human bacterial pathogens.     

Effects of external pelvic compression on form closure, force closure, and neuromotor control of the lumbopelvic spine--a systematic review

Optimal lumbopelvic stability is a function of form closure (joint anatomy), force closure (additional compressive forces acting across the joints) and neuromotor control. Impairment of any of these mechanisms can result in pain, instability, altered lumbopelvic kinematics, and changes in muscle strength and motor control. External pelvic compression (EPC) has been hypothesised to have an effect on force closure and neuromotor control. However, the specific application parameters (type, location and force) and hypothesized effects of EPC are unclear. Thus, a systematic review was conducted to summarize the in vivo and in vitro effects of EPC. Eighteen articles met the eligibility criteria, with quality ranging from 33% to 72% based on a modified Downs and Black index. A modified van Tulder's rating system was used to ascertain the level of evidence synthesised from this review. There is moderate evidence to support the role of EPC in decreasing laxity of the sacroiliac joint, changing lumbopelvic kinematics, altering selective recruitment of stabilizing musculature, and reducing pain. There is limited evidence for effects of EPC on decreasing sacral mobility, and affecting strength of muscles surrounding the SIJ, factors which require further investigation.     

The flavonoid fisetin attenuates postischemic immune cell infiltration, activation and infarct size after transient cerebral middle artery occlusion in mice

The development of the brain tissue damage in ischemic stroke is composed of an immediate component followed by an inflammatory response with secondary tissue damage after reperfusion. Fisetin, a flavonoid, has multiple biological effects, including neuroprotective and antiinflammatory properties. We analyzed the effects of fisetin on infarct size and the inflammatory response in a mouse model of stroke, temporary middle cerebral artery occlusion, and on the activation of immune cells, murine primary and N9 microglial and Raw264.7 macrophage cells and human macrophages, in an in vitro model of inflammatory immune cell activation by lipopolysaccharide (LPS). Fisetin not only protected brain tissue against ischemic reperfusion injury when given before ischemia but also when applied 3 hours after ischemia. Fisetin also prominently inhibited the infiltration of macrophages and dendritic cells into the ischemic hemisphere and suppressed the intracerebral immune cell activation as measured by intracellular tumor necrosis factor α (TNFα) production. Fisetin also inhibited LPS-induced TNFα production and neurotoxicity of macrophages and microglia in vitro by suppressing nuclear factor κB activation and JNK/Jun phosphorylation. Our findings strongly suggest that the fisetin-mediated inhibition of the inflammatory response after stroke is part of the mechanism through which fisetin is neuroprotective in cerebral ischemia.     

A high-resolution large area serotonin map of a live rat brain section

We employ three-photon microscopy to produce a high-resolution map of serotonin autofluorescence in a rat midbrain section (covering more than half of the brain), to quantitatively characterize serotonin distribution and release in different areas of a live brain slice. The map consists of a tiling of approximately 160 contiguous optical images (covering an area of approximately 27 mm with sub-mum resolution in 20 min), and is recorded before and after inducing depolarization. We observe that the total serotonin exocytosed from the somata in the raphe is quantitatively comparable with regions containing a high density of serotonergic processes. Our results demonstrate that high-resolution, wide-area, dynamic neurotransmitter mapping is now possible.