Mice lacking ghrelin receptors resist the development of diet-induced obesity

Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor (GHSR; ghrelin receptor). Since its discovery, accumulating evidence has suggested that ghrelin may play a role in signaling and reversing states of energy insufficiency. For example, ghrelin levels rise following food deprivation, and ghrelin administration stimulates feeding and increases body weight and adiposity. However, recent loss-of-function studies have raised questions regarding the physiological significance of ghrelin in regulating these processes. Here, we present results of a study using a novel GHSR-null mouse model, in which ghrelin administration fails to acutely stimulate food intake or activate arcuate nucleus neurons. We show that when fed a high-fat diet, both female and male GHSR-null mice eat less food, store less of their consumed calories, preferentially utilize fat as an energy substrate, and accumulate less body weight and adiposity than control mice. Similar effects on body weight and adiposity were also observed in female, but not male, GHSR-null mice fed standard chow. GHSR deletion also affected locomotor activity and levels of glycemia. These findings support the hypothesis that ghrelin-responsive pathways are an important component of coordinated body weight control. Moreover, our data suggest that ghrelin signaling is required for development of the full phenotype of diet-induced obesity.     

Inpatient and postdischarge rehabilitation services provided in the first year after spinal cord injury: findings from the SCIRehab Study

Whiteneck GG, Gassaway J, Dijkers MP, Lammertse DP, Hammond F, Heinemann AW, Backus D, Charlifue S, Ballard PH, Zanca JM. Inpatient and postdischarge rehabilitation services provided in the first year after spinal cord injury: findings from the SCIRehab study.

Objective

To examine the amount and type of therapy services received in inpatient and postdischarge settings during the first year after spinal cord injury (SCI).

Design

Prospective observational longitudinal cohort design. Data were obtained from systematic recording of interventions by clinicians and from patient interview.

Setting

Inpatient and postdischarge rehabilitation programs.

Participants

Patients (N=493) with traumatic SCI admitted to 6 rehabilitation centers participating in the SCIRehab study.

Interventions

Not applicable.

Main Outcome Measures

Hours of therapy by physical therapy (PT), occupational therapy (OT), speech therapy, recreation therapy, psychology, social work/case management, and nursing education during initial inpatient rehabilitation and postdischarge up to the first anniversary of injury. Inpatient data were collected prospectively by the treating clinicians; postdischarge service data were collected by patient self-report during follow-up interviews.

Results

Of the total hours spent on these rehabilitation interventions during the first year after injury, 44% occurred after discharge from inpatient rehabilitation. Participants received 56% of their PT hours after discharge and 52% of their OT hours, but only a minority received any postdischarge services from other rehabilitation disciplines. While wide variation was found in the total hours of inpatient treatment across all disciplines, the variation in the total hours of postdischarge services was greater, with the interquartile range of postdischarge services being twice that of the inpatient services.

Conclusions

SCI rehabilitation is often given in a care continuum, with inpatient rehabilitation being only the beginning. Reductions in inpatient SCI rehabilitation length of stay are well documented, but the postdischarge services that may replace some inpatient treatment appear to be greater than previously reported. The availability and impact of postdischarge care should be studied in greater detail to capture the wide array of postdischarge services and outcomes.     

Protection against Klebsiella pneumoniae Using Lithium Chloride in an Intragastric Infection Model

Intragastric Klebsiella pneumoniae infections of mice can cause liver abscesses, necrosis of liver tissues, and bacteremia. Lithium chloride, a widely prescribed drug for bipolar mood disorder, has been reported to possess anti-inflammatory properties. Using an intragastric infection model, the effects of LiCl on K. pneumoniae infections were examined. Providing mice with drinking water containing LiCl immediately after infection protected them from K. pneumoniae-induced death and liver injuries, such as necrosis of liver tissues, as well as increasing blood levels of aspartate aminotransferase and alanine aminotransferase, in a dose-dependent manner. LiCl administered as late as 24 h postinfection still provided protection. Monitoring of the LiCl concentrations in the sera of K. pneumoniae-infected mice showed that approximately 0.33 mM LiCl was the most effective dose for protecting mice against infections, which is lower than the clinically toxic dose of LiCl. Surveys of bacterial counts and cytokine expression levels in LiCl-treated mice revealed that both were effectively inhibited in blood and liver tissues. Using in vitro assays, we found that LiCl (5 μM to 1 mM) did not directly interfere with the growth of K. pneumoniae but made K. pneumoniae cells lose the mucoid phenotype and become more susceptible to macrophage killing. Furthermore, low doses of LiCl also partially enhanced the bactericidal activity of macrophages. Taken together, these data suggest that LiCl is an alternative therapeutic agent for K. pneumoniae-induced liver infections.