Glycerol monolaurate inhibits lipase production by clinical ocular isolates without affecting bacterial cell viability

PURPOSE. We sought to determine the relative lipase production of a range of ocular bacterial isolates and to assess the efficacy of glycerol monolaurate (GML) in inhibiting this lipase production in high lipase-producing bacteria without affecting bacterial cell growth. METHODS. Staphylococcus aureus, Staphylococcus epidermidis, Propionibacterium acnes, and Corynebacterium spp. were inoculated at a density of 106/mL in varying concentrations of GML up to 25 μg/mL for 24 hours at 378C with constant shaking. Bacterial suspensions were centrifuged, bacterial cell density was determined, and production of bacterial lipase was quantified using a commercial lipase assay kit. RESULTS. Staphylococcus spp. produced high levels of lipase activity compared with P. acnes and Corynebacterium spp. GML inhibited lipase production by Staphylococcal spp. in a dosedependent manner, with S. epidermidis lipase production consistently more sensitive to GML than S. aureus. Glycerol monolaurate showed significant (P \u3c 0.05) lipase inhibition above concentrations of 15 μg /mL in S. aureus and was not cytotoxic up to 25 μg /mL. For S. epidermidis, GML showed significant (P \u3c 0.05) lipase inhibition above 7.5 μg /mL. CONCLUSIONS. Lipase activity varied between species and between strains. Staphylococcal spp. produced higher lipase activity compared with P. acnes and Corynebacterium spp. Glycerol monolaurate inhibited lipase production by S. aureus and S. epidermidis at concentrations that did not adversely affect bacterial cell growth. GML can be used to inhibit ocular bacterial lipase production without proving detrimental to commensal bacteria viability

Amyloid precursor proteins, neural differentiation in pluripotent stem cells and relevance to Alzheimer's disease

Alzheimer’s disease is a leading cause of age-related dementia that is characterized by an extensive loss of neurons and synaptic transmission. The pathological hallmarks of AD are: neurofibrillary tangles and deposition of β-amyloid (Aβ) plaques. Previous research has investigated how Aβ fragments disrupt synaptic mechanisms in the vulnerable regions of the brain. There is a tremendous potential for stem cell technology to extend upon this research not only in terms of developing therapeutic applications, but also in modeling AD. Indeed, the advent of induced pluripotent stem cell technology has opened up exciting new avenues for generating patient and disease-specific cell lines from somatic cells that may be used to model AD. Amyloid precursor protein (APP) is a key protein in neuronal development and this article reviews the role of APP in AD. Stem cell technology offers the opportunity to make use of APP in the directed differentiation of induced pluripotent stem cells into functional neurons, a process that may help generate a model of AD and thereby facilitate an understanding of the mechanisms underlying this disease

The role of pancreatic polypeptide in the regulation of energy homeostasis

Imbalances in normal regulation of food intake can cause obesity and related disorders. Inadequate therapies for such disorders necessitate better understanding of mechanisms that regulate energy homeostasis. Pancreatic polypeptide (PP), a robust anorexigenic hormone, effectively modulates food intake and energy homeostasis, thus potentially aiding anti-obesity therapeutics. Intra-gastric and intra-intestinal infusion of nutrients stimulate PP secretion from the gastrointestinal tract, leading to vagal stimulation that mediates complex actions via the neuropeptide Y4 receptor in arcuate nucleus of the hypothalamus, subsequently activating key hypothalamic nuclei and dorsal vagal complex of the brainstem to influence energy homeostasis and body composition. Novel studies indicate affinity of PP for the relatively underexplored neuropeptide y6 receptor, mediating actions via the suprachiasmatic nucleus and pathways involving vasoactive intestinal polypeptide and insulin like growth factor 1. This review highlights detailed mechanisms by which PP mediates its actions on energy balance through various areas in the brain

RANKL reduces body weight and food intake via the modulation of hypothalamic NPY/CART expression

The receptor activator of nuclear factor-κB ligand (RANKL) modulates energy metabolism. However, how RANKL regulates energy homeostasis is still not clear. This study aims to investigate the central mechanisms by which central administration of RANKL inhibits food intake and causes weight loss in mice. We carried out a systematic and in-depth analysis of the neuronal pathways by which RANKL mediates catabolic effects. After intracerebroventricle (i.c.v.) injection of RANKL, the expression of neuropeptide Y (NPY) mRNA in the Arc was significantly decreased, while the CART mRNA expression dramatically increased in the Arc and DMH. However, the agouti-related protein (AgRP) and pro-opiomelanocortin (POMC) mRNA had no significant changes compared with control groups. Together, the results suggest that central administration of RANKL reduces food intake and causes weight loss via modulating the hypothalamic NPY/CART pathways

Cold exposure promotes obesity and impairs glucose homeostasis in mice subjected to a highfat diet

Cold exposure is considered to be a form of stress and has various adverse effects on the body. The present study aimed to investigate the effects of chronic daily cold exposure on food intake, body weight, serum glucose levels and the central energy balance regulatory pathway in mice fed with a high‑fat diet (HFD). C57BL/6 mice were divided into two groups, which were fed with a standard chow or with a HFD. Half of the mice in each group were exposed to ice‑cold water for 1 h/day for 7 weeks, while the controls were exposed to room temperature. Chronic daily cold exposure significantly increased energy intake, body weight and serum glucose levels in HFD‑fed mice compared with the control group. In addition, 1 h after the final cold exposure, c‑fos immunoreactivity was significantly increased in the central amygdala of HFD‑fed mice compared with HFD‑fed mice without cold exposure, indicating neuronal activation in this brain region. Notably, 61% of these c‑fos neurons co‑expressed the neuropeptide Y (NPY), and the orexigenic peptide levels were significantly increased in the central amygdala of cold‑exposed mice compared with control mice. Notably, cold exposure significantly decreased the anorexigenic brain‑derived neurotropic factor (BDNF) messenger RNA (mRNA) levels in the ventromedial hypothalamic nucleus and increased growth hormone releasing hormone (GHRH) mRNA in the paraventricular nucleus. NPY‑ergic neurons in the central amygdala were activated by chronic cold exposure in mice on HFD via neuronal pathways to decrease BDNF and increase GHRH mRNA expression, possibly contributing to the development of obesity and impairment of glucose homeostasis

Reduced serum levels of oestradiol and brain derived neurotrophic factor in both diabetic women and HFD-feeding female mice

The estrogen levels in the pre and post menstrual phases interact with brain-derived neurotrophic factor in a complex manner, which influences the overall state of the body. To study the role of oestradiol and brain-derived neurotrophic factor in modulating obesity related type 2 diabetes and the interactions between two factors, we enrolled 15 diabetic premenopausal women and 15 diabetic postmenopausal women respectively, the same number of healthy pre and postmenopausal women were recruited as two control groups. The fasting blood glucose, insulin, lipids, estrogen, and brain-derived neurotrophic factor levels were measured through clinical tests. Additionally, we set up obese female mouse model to mimic human trial stated above, to verify the relationship between estrogen and brain-derived neurotrophic factor. Our findings revealed that there is a moderately positive correlation between brain-derived neurotrophic factor and oestradiol in females, and decreased brain-derived neurotrophic factor may worsen impaired insulin function. The results further confirmed that high fat diet-fed mice which exhibited impaired glucose tolerance, showed lower levels of oestradiol and decreased expression of brain-derived neurotrophic factor mRNA in the ventromedial hypothalamus. The level of brain-derived neurotrophic factor reduced on condition that the level of oestradiol is sufficiently low, such as women in postmenopausal period, which aggravates diabetes through feeding-related pathways. Increasing the level of brain-derived neurotrophic factor may help to alleviate the progression of the disease in postmenopausal women with diabetes