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Obesity is a significant risk factor in the pathogenesis of obstructive sleep apnoea (OSA) altering airway anatomy and collapsibility, and respiratory control. The association between obesity and OSA has led to an increasing focus on the role of weight loss as a potential treatment for OSA. To date, most discussion of obesity and OSA assumes a one-way cause and effect relationship, with obesity contributing to the pathogenesis of OSA. However, OSA itself may contribute to the development of obesity. OSA has a potential role in the development and reinforcement of obesity via changes to energy expenditure during sleep and wake periods, dietary habits, the neurohormonal mechanisms that control satiety and hunger, and sleep duration arising from fragmented sleep. Thus, there is emerging evidence that OSA itself feeds back into a complex mechanism that leads either to the development or reinforcement of the obese state. Whilst current evidence does not confirm that treatment of OSA directly influences weight loss, it does suggest that the potential role OSA plays in obesity and weight loss deserves further research.

Repetitive drug/ethanol (EtOH) binge-like consumption during pre-addictive stages favors a transition to addiction in vulnerable organisms. Experimental evidence points to the therapeutic and preventive effects of environmental enrichment (EE) on drug and EtOH addiction; however, little is known regarding EE modulation of binge-like consumption in non-dependent organisms. Here, we explore the impact of early EE on binge-like EtOH consumption: (1) we test whether early EE exposure prevents binge-like EtOH intake (20% v/v) in adult mice under an intermittent drinking in the dark (iDID) schedule; (2) we evaluate the therapeutic effects of EE housing conditions on binge-like EtOH consumption in adult animals; and (3) we compare novelty-seeking and compulsive-like behaviors, and anxiety-like behavior, as measured by the Hole Board (HB) and Elevated Plus Maze (EPM) tests, respectively, in adult EE/standard environment (SE) animals. Adolescent (postnatal day 28; PND28) mice were randomly allocated to two housing conditions (4 animals/cage): EE or SE. At PND67 all the animals were exposed to a schedule of EtOH binge-like iDID. On PND92 half of the animals in each environmental condition (EE and SE) were randomly allocated to two subgroups in a crossover design, where environmental conditions were kept similar to those previously experienced or switched, finally leading to four experimental conditions: EE-EE, EE-SE, SE-SE, and SE-EE. EtOH binge-like consumption continued until PND140, when EPM and HB tests were finally conducted. The main observations were: (1) EE-reared mice showed lower EtOH binge-like intake than SE-reared mice during adulthood, which supports a protective role for EE. (2) when adult EtOH drinking SE-reared mice were switched to EE conditions, a reduction in EtOH binge-like consumption was observed, suggesting a therapeutic role for EE; however, losing EE during adulthood triggered a progressive increase in EtOH binge-like intake. Moreover, (3) EE-housed adult animals with long-term exposure to EtOH binge-drinking showed lower anxiety-like, compulsive-like, and novelty-seeking behaviors than SE-housed mice, irrespective of the specific housing conditions during adolescence. We discuss the primary impact of EE on anxiety-like neurobehavioral brain systems through which it secondarily modulates EtOH binge-like drinking.

Key points Prenatal alcohol exposure has the potential to affect fetal development and programme chronic disease in offspring. Previous preclinical models typically use high, chronic doses of alcohol throughout pregnancy to examine effects on offspring, particularly on the brain and behaviour. In this study we use a rat model of moderate, acute, prenatal alcohol exposure to determine if this can be detrimental to maintenance of glucose homeostasis in adolescent and adult offspring. Although female offspring were relatively unaffected, there was evidence of insulin resistance in 6‐month‐old male offspring exposed to prenatal alcohol, suggestive of a pre‐diabetic state. This result suggests that even a relatively low‐dose, acute exposure to alcohol during pregnancy can still programme metabolic dysfunction in a sex‐specific manner. AbstractAlcohol consumption is highly prevalent amongst women of reproductive age. Given that approximately 50% of pregnancies are unplanned, alcohol has the potential to affect fetal development and programme chronic disease in offspring. We examined the effect of an acute but moderate prenatal alcohol exposure (PAE) on glucose metabolism, lipid levels and dietary preference in adolescent and/or adult rat offspring. Pregnant Sprague–Dawley rats received an oral gavage of ethanol (1 g kg−1 maternal body weight, n = 9 dams) or an equivalent volume of saline (control, n = 8 dams) at embryonic days 13.5 and 14.5. PAE resulted in a blood alcohol concentration of 0.05–0.06% 1 h post‐gavage in dams. Fasting blood glucose concentration was not affected by PAE in offspring at any age, nor were blood glucose levels during a glucose tolerance test (GTT) in 6‐month‐old offspring (P > 0.5). However, there was evidence of insulin resistance in PAE male offspring at 6 months of age, with significantly elevated fasting plasma insulin (P = 0.001), a tendency for increased first phase insulin secretion during the GTT and impaired glucose clearance following an insulin challenge (P = 0.007). This was accompanied by modest alterations in protein kinase B (AKT) signalling in adipose tissue. PAE also resulted in reduced calorie consumption by offspring compared to controls (P = 0.04). These data suggest that a relatively low‐level, acute PAE programmes metabolic dysfunction in offspring in a sex‐specific manner. These results highlight that alcohol consumption during pregnancy has the potential to affect the long‐term health of offspring.

The pervasive use of refined sugars in highly accessible, palatable foods and persistent exposure to reinforcing food‐associated cues has contributed to overconsumption of sugar‐rich diets and the current obesity epidemic in Western society. We have shown previously that brain relaxin‐3 mRNA levels positively correlate with sucrose and alcohol intake, and that central antagonism of relaxin‐3 receptors (RXFP3) attenuates alcohol self‐administration and alcohol‐seeking in rats, but food‐seeking behaviour and palatable food consumption in mice. To further examine the relationship between motivated appetitive behaviours and relaxin‐3/RXFP3 signalling, we investigated the effect of Rxfp3 gene deletion in C57BL/6J mice on sucrose and alcohol self‐administration and cue‐induced reinstatement (RNST) of sucrose‐ and alcohol‐seeking. Acquisition and maintenance of sucrose and alcohol self‐administration was assessed in male wild‐type (WT) and Rxfp3 knockout (KO) (C57BL/6JRXFP3TM1/DGen) littermate mice using fixed ratio (FR) schedules of reinforcement. Mice were subsequently challenged with a progressive ratio (PR) test to measure motivation and, following extinction training, re‐exposed to reward‐associated cues to evaluate RNST of active lever‐responding. Wild‐type and Rxfp3 KO mice displayed similar acquisition of FR1 sucrose self‐administration, but Rxfp3 KO mice responded less when the instrumental requirement was increased to FR3. These mice also showed a lower breakpoint for sucrose and attenuated cue‐induced RNST of sucrose‐seeking. Notably, no marked genotype differences in alcohol‐responding were observed. In mice, endogenous relaxin‐3/RXFP3 signalling promotes self‐administration of sucrose under high response requirements and cue‐induced RNST of sucrose‐seeking, but does not apparently regulate motivation to consume alcohol or alcohol‐seeking behaviour.

Obesity is a growing global concern with strong associations with cardiovascular disease, cancer and type-2 diabetes. Although various genome-wide association studies have identified more than 40 genes associated with obesity, these genes cannot fully explain the heritability of obesity, suggesting there may be other contributing factors, including epigenetic effects.We performed genome wide DNA methylation profiling comparing normal-weight and obese 9-13 year old children to investigate possible epigenetic changes correlated with obesity. Of note, obese children had significantly lower methylation levels at a CpG site located near coronin 7 (CORO7), which encodes a tryptophan-aspartic acid dipeptide (WD)-repeat containing protein most likely involved in Golgi complex morphology and function. Anatomical profiling of coronin 7 (Coro7) mRNA expression in mice revealed that it is highly expressed in appetite and energy balance regulating regions, including the hypothalamus, striatum and locus coeruleus, the main noradrenergic brain site. Interestingly, we found that food deprivation in mice downregulates hypothalamic Coro7 mRNA levels, and injecting ethanol, an appetite stimulant, increased the number of Coro7 expressing cells in the locus coeruleus. Finally, by employing the genetically-tractable Drosophila melanogaster model we were able to demonstrate an evolutionarily conserved metabolic function for the CORO7 homologue pod1. Knocking down the pod1 in the Drosophila adult nervous system increased their resistance to starvation. Furthermore, feeding flies a high-calorie diet significantly increased pod1 expression.We conclude that coronin 7 is involved in the regulation of energy homeostasis and this role stems, to some degree, from the effect on feeding for calories and reward.

Leptin regulates body weight in mice by decreasing appetite and increasing sympathetic nerve activity (SNA), which increases energy expenditure in interscapular brown adipose tissue (iBAT). Diet-induced obese mice (DIO) are resistant to the anorectic actions of leptin. We evaluated whether leptin still stimulated sympathetic outflow in DIO mice. We measured iBAT temperature as a marker of SNA. We found that obese hyperleptinemic mice have higher iBAT temperature than mice on regular diet. Conversely, obese leptin-deficientob/obmice have lower iBAT temperature. Additionally, leptin increased SNA in obese (DIO andob/ob) and control mice, despite DIO mice being resistant to anorectic action of leptin. We demonstrated that neurons in the dorsomedial hypothalamus (DMH) of DIO mice mediate the thermogenic responses to hyperleptinemia in obese mammals because blockade of leptin receptors in the DMH prevented the thermogenic effects of leptin.Peripheral Melotan II (MTII) injection increased iBAT temperature, but it was blunted by blockade of DMH melanocortin receptors (MC4Rs) by injecting agouti-related peptide (AgRP) directly into the DMH, suggesting a physiological role of the DMH on temperature regulation in animals with normal body weight. Nevertheless, obese mice without a functional melanocortin system (MC4R KO mice) have an increased sympathetic outflow to iBAT compared with their littermates, suggesting that higher leptin levels drive sympathoexcitation to iBAT by a melanocortin-independent pathway.Because the sympathetic nervous system contributes in regulating blood pressure, heart rate, and hepatic glucose production, selective leptin resistance may be a crucial mechanism linking adiposity and metabolic syndrome.

Abstract: In avian species it has been difficult to elucidate the precise role of melatonin in the control of reproductive cycles. We have investigated ways of administering melatonin to immature chickens and laying hens to achieve physiological levels and patterns in blood simulating either short or long photoperiods. Melatonin was administered orally using different doses and various ways of applying melatonin to the feed. For subcutaneous injections, melatonin was suspended in propylene glycol or grape seed oil. Melatonin always appeared in the first blood samples taken within an hour of administration. When melatonin was absorbed into feed pellets or whole wheat, a high initial plasma concentration was reached. followed by a rapid decrease over the ensuing 2–3 hr, but was still detectable as long as 24 hr after administration. For example, doses of 300 μg/kg produced 15 nM, which is more than ten times higher than the nocturnal peak concentration. When melatonin was absorbed into cracked wheat grains that were subsequently washed with ethanol, the initial transitory peak was eliminated, levels in plasma were sustained for at least 12 hr in the normal nocturnal range (750 pM), and no melatonin (< 60 pM) was present 18 hr later. When injected (2 μg/bird), concentrations peaked (610 pM) within 30 min and decreased rapidly over the next 2–3 hr. It was concluded that melatonin‐treated. ethanol‐rinsed cracked wheat grains can be used to experimentally mimic long‐night plasma melatonin patterns. Injections may be useful for mimicking the melatonin patterns of very short nights in chickens experiencing constant light.