Acute effects of acylated and unacylated ghrelin on total and high molecular weight adiponectin inmorbidly obese subjects.

BACKGROUND: Energy homeostasis and body weight are regulated by a highly complex network involving the brain, the digestive tract, and white adipose tissue (WAT). Knowledge about signaling pathways connecting digestive tract and WAT is limited. Gut hormone ghrelin and adipokine adiponectin are both decreased in obesity and they share a potent effect on insulin sensitivity: both adiponectin and the combination of acylated (AG) and unacylated ghrelin (UAG) improve insulin sensitivity. AIM: In the present study, we evaluated whether acute administration of UAG alone or combined with AG affects adiponectin concentrations. SUBJECTS AND METHODS: Eight morbidly obese non-diabetic subjects were treated with either UAG 200 µg, UAG 100 µg + AG 100 µg (Comb), or placebo in 3 episodes in a double blind randomized cross-over design. Study medication was administered as single iv bolus injections at 09:00 h after an overnight fast. High molecular weight (HMW) and total adiponectin, glucose, insulin, and total ghrelin and AG were measured up to 1 h after administration. RESULTS: HMW and total adiponectin concentrations did not change after administration of either UAG or Comb, nor were they different from placebo. Insulin concentrations decreased significantly after acute administration of Comb, reaching a minimum at 20 min: 58.2 ± 3.9% of baseline. CONCLUSIONS: Acute iv administration of UAG and the combination of UAG and AG in morbidly obese non-diabetic subjects without overt diabetes does not affect total or HMW adiponectin concentrations, neither directly nor indirectly by changing insulin concentrations.

Lipopolysaccharide modifies amiloride-sensitive Na+ transport processes across human airway cells: role of mitogen-activated protein kinases ERK 1/2 and 5.

Bacterial lipopolysaccharides (LPS) are potent inducers of proinflammatory signaling pathways via the activation of nuclear factor-kappa B (NF-kappaB) and mitogen-activated protein kinase (MAPK), causing changes in the processes that control lung fluid homeostasis and contributing to the pathogenesis of lung disease. In human H441 airway epithelial cells, incubation of cells with 15 microg ml(-1) LPS caused a significant reduction in amiloride-sensitive I (sc) from 15 +/- 2 to 8 +/- 2 microA cm(-2) (p = 0.01, n = 13) and a shift in IC(50) amiloride of currents from 6.8 x 10(-7) to 6.4 x 10(-6) M. This effect was associated with a decrease in the activity of 5 pS, highly Na(+) selective, amiloride-sensitive <1 microM channels (HSC) and an increase in the activity of approximately 18 pS, nonselective, amiloride-sensitive >10 microM cation channels (NSC) in the apical membrane. LPS decreased alphaENaC mRNA and protein abundance, inferring that LPS inhibited alphaENaC gene expression. This correlated with the decrease in HSC activity, indicating that these channels, but not NSCs, were comprised of at least alphaENaC protein. LPS increased NF-kappaB DNA binding activity and phosphorylation of extracellular signal-related kinase (ERK)1/2, but decreased phosphorylation of ERK5 in H441 cells. Pretreatment of monolayers with PD98059 (20 microM) inhibited ERK1/2 phosphorylation, promoted phosphorylation of ERK5, increased alphaENaC protein abundance, and reversed the effect of LPS on I (sc) and the shift in amiloride sensitivity. Inhibitors of NF-kappaB activation were without effect. Taken together, our data indicate that LPS acts via ERK signaling pathways to decrease alphaENaC transcription, reducing HSC/ENaC channel abundance, activity, and transepithelial Na(+) transport in H441 airway epithelial cells.

The circulating concentration and ratio of total and high molecular weight adiponectin in post-menopausal women with and without osteoporosis and its association with body mass index and biochemical markers of bone metabolism.

OBJECTIVES: There is increasing evidence suggesting that adiponectin plays a role in the regulation of bone metabolism. DESIGN AND METHODS: This was a cross-sectional study of 34 post-menopausal women with and 37 without osteoporosis. All subjects had body mass index (BMI), bone mineral density (BMD), total-, high molecular weight (HMW)-adiponectin and their ratio, osteoprotegerin (OPG), a marker of bone resorption (betaCTX) and formation (P1NP) measured. RESULTS: We observed a positive correlation between BMI and BMD (r=0.44, p<0.001). When normalised for BMI, total-, HMW-adiponectin concentrations and HMW/total-adiponectin ratio were significantly lower in obese compared to lean subjects but there was no difference between those with or without osteoporosis. There were significant negative correlations between HMW/total-adiponectin ratio and BMI (r=-0.27, p=0.030) and with OPG (r=-0.44, p<0.001). CONCLUSIONS: Our data suggests that there is no significant difference in the circulating concentration of fasting early morning total- or HMW-adiponectin in post-menopausal women with or without osteoporosis. The correlation between HMW/total-adiponectin ratio and OPG may indicate that adiponectin could influence bone metabolism by altering osteoblast production of OPG thereby affecting osteoclasts mediated bone resorption.