Characterization of cold-induced remodelling reveals depot-specific differences across and within brown and white adipose tissues in mice.

AIM: Brown and beige adipose tissues dissipate energy in the form of heat via mitochondrial uncoupling protein 1, defending against hypothermia and potentially obesity. The latter has prompted renewed interest in understanding the processes involved in browning to realize the potential therapeutic benefits. To characterize the temporal profile of cold-induced changes and browning of brown and white adipose tissues in mice. METHODS: Male C57BL/6J mice were singly housed in conventional cages under cold exposure (4 °C) for 1, 2, 3, 4, 5 and 7 days. Food intake and body weight were measured daily. Interscapular brown adipose tissue (iBAT), inguinal subcutaneous (sWAT) and epididymal white adipose tissue (eWAT) were harvested for histological, immunohistochemical, gene and protein expression analysis. RESULTS: Upon cold exposure, food intake increased, whilst body weight and adipocyte size were found to be transiently reduced. iBAT mass was found to be increased, whilst sWAT and eWAT were found to be transiently decreased. A combination of morphological, genetic (Ucp-1, Pgc-1α and Elov13) and biochemical (UCP-1, PPARγ and aP2) analyses demonstrated the depot-specific remodelling in response to cold exposure. CONCLUSION: Our results demonstrate the differential responses to cold-induced changes across discrete BAT and WAT depots and support the notion that the effects of short-term cold exposure are achieved by expansion, activation and increasing thermogenic capacity of iBAT, as well as browning of sWAT and, to a lesser extent, eWAT.

Acute sleep deprivation delays the glucagon-like peptide 1 peak response to breakfast in healthy men.

OBJECTIVE: Previous experiments have demonstrated that acute sleep loss impairs glucose homeostasis and increases food intake in humans. The incretin hormone glucagon-like peptide 1 (GLP-1) enhances postprandial insulin secretion and promotes satiety. Hypothesizing that the detrimental metabolic effects of sleep curtailment imply alterations in GLP-1 signaling, we investigated 24-h serum total GLP-1 concentrations during total sleep deprivation (TSD) and a normal sleep/wake cycle (comprising ∼8 h of sleep) in 12 healthy young men. METHODS: Sessions started at 1800 h, and subjects were provided with standardized meals. Assessments of serum GLP-1 took place in 1.5- to 3-h intervals, focusing on the response to breakfast intake (3.8 MJ). RESULTS: Across conditions, 24-h concentration profiles of GLP-1 were characterized by the expected postprandial increases (P<0.001). Although there were no differences in magnitude between conditions (P>0.11), the postprandial GLP-1 peak response to breakfast intake was delayed by ∼90 min following sleep loss in comparison with regular sleep (P<0.02). CONCLUSIONS: RESULTS indicate that acute TSD exerts a mild, but discernible effect on the postprandial dynamics of circulating GLP-1 concentrations in healthy men.

A panel study of air pollution in subjects with heart failure: negative results in treated patients.

OBJECTIVES: To investigate preclinical adverse effects of ambient particulate air pollution and nitrogen oxides in patients with heart failure. METHODS: A cohort of 132 non-smoking patients living in Aberdeen, Scotland, with stable chronic heart failure were enrolled in a repeated-measures panel study. Patients with atrial fibrillation or pacemakers were excluded. Participants were studied for 3 days every 2 months for up to 1 year with monitoring of pollutant exposure and concurrent measurements of pathophysiological responses. Measurements included daily area concentration of particulate matter with a median aerodynamic diameter of <10 micrometres (PM(10)), particle number concentration (PNC) and nitrogen oxides; daily estimated personal concentration of particulate matter with a median aerodynamic diameter of <2.5 micrometres (PM(2.5)) and PNC exposures; and 3-day cumulative personal nitrogen dioxide (NO(2)). Concurrent meteorological data were recorded. Blood was taken at the end of each 3-day block for assays of markers of endothelial activation, inflammation and coagulation. Cardiac rhythm was monitored by ambulatory Holter monitor during the final 24 h of each block. RESULTS: The average 24 h background ambient PM(10) ranged from 7.4 to 68 microg.m(-3) and PNC from 454 to 11 283 particles.cm(-3). No associations were demonstrated between the incidence of arrhythmias, heart rate variability or haematological/biochemical measures and any variations in pollutant exposures at any lags. CONCLUSION: Assuming that low-level pollution affects the parameters measured, these findings may suggest a beneficial effect of modern cardioprotective therapy, which may modify responses to external risk factors. Widespread use of such drugs in susceptible populations may in future reduce the adverse effects of air pollution on the heart.

A prostaglandin f(2alpha) analog induces suppressors of cytokine signaling-3 expression in the corpus luteum of the pregnant rat: a potential new mechanism in luteolysis.

PRL and placental lactogen (PL) play key roles in maintaining the rodent corpus luteum through pregnancy. Suppressors of cytokine signaling (SOCS) have been shown to decrease cell sensitivity to cytokines, including PRL, and so here we have addressed the issue of whether luteolysis induced by prostaglandin F(2alpha) (PGF(2alpha)) might up-regulate SOCS proteins to inhibit PRL signaling. In d 19 pregnant rats, cloprostenol, a PGF(2alpha) analog, rapidly induced transcripts for SOCS-3 and, to a lesser extent, SOCS-1. We also found increased SOCS-3 protein in the ovary by immunoblot and in the corpus luteum by immunohistochemistry. Increased SOCS-3 expression was preceded by an increase in STAT3 tyrosine phosphorylation 10 min after cloprostenol injection and was maintained for 4 h, as determined by gel shift and immunohistochemistry. Induction of SOCS-3 was accompanied by a sharp decrease in active STAT5, as determined by gel-shift assay and by loss of nuclear localized STAT5. Four hours after cloprostenol administration, the corpus luteum was refractory to stimulation of STAT5 by PRL administration, and this was not due to down-regulation of PRL receptor. Therefore, induction of SOCS-3 by PGF(2alpha) may be an important element in the initiation of luteolysis via rapid suppression of luteotropic support from PL.

Prolactin-releasing peptide in the ewe: cDNA cloning, mRNA distribution and effects on prolactin secretion in vitro and in vivo.

RT-PCR followed by 5'- and 3'- rapid amplification of cDNA ends was used to clone and sequence ovine prolactin-releasing peptide (PrRP). The cDNA was characterised by short 5'- and 3'-untranslated regions and a GC-rich (71%) coding region. The nucleotide and deduced amino acid sequences for the coding region showed 95.6 and 94.9% identity with bovine PrRP but the amino acid sequence of PrRP31 was conserved between these species. Northern blot analysis and RT-PCR showed that, as in the rat, the peptide was more abundantly expressed in the brainstem than the hypothalamus. However, in the ovine hypothalamus, PrRP mRNA expression was more widespread than in the rat, with expression detected in both rostral and caudal parts of the mediobasal hypothalamus. The effects of synthetic ovine PrRP on prolactin secretion both in vitro and in vivo were also examined. In primary cultures of sheep pituitary cells, PrRP significantly (P<0.01) increased prolactin concentrations in the culture medium but the response was not observed in every experiment and was only seen when pituitary glands were dispersed with collagenase rather than trypsin. PrRP was much less potent than TRH which caused a significant (P<0.01) two- to threefold increase in prolactin concentrations in every experiment. Intravenous (10 and 50 nmol) or intracerebroventricular (10 and 50 nmol) injection of PrRP had no significant effect on either plasma prolactin concentration or pulsatile LH secretion whereas intravenous injection of TRH (10 nmol) produced a highly significant (P<0.01) and more than sevenfold stimulation of plasma prolactin concentrations. In conclusion, these results suggest that PrRP is unlikely to be an important prolactin-releasing factor in this species.