Subcutaneous fat transplantation alleviates diet-induced glucose intolerance and inflammation in mice.

AIMS/HYPOTHESIS: Adipose tissue (AT) distribution is a major determinant of mortality and morbidity in obesity. In mice, intra-abdominal transplantation of subcutaneous AT (SAT) protects against glucose intolerance and insulin resistance (IR), but the underlying mechanisms are not well understood. METHODS: We investigated changes in adipokines, tissue-specific glucose uptake, gene expression and systemic inflammation in male C57BL6/J mice implanted intra-abdominally with either inguinal SAT or epididymal visceral AT (VAT) and fed a high-fat diet (HFD) for up to 17 weeks. RESULTS: Glucose tolerance was improved in mice receiving SAT after 6 weeks, and this was not attributable to differences in adiposity, tissue-specific glucose uptake, or plasma leptin or adiponectin concentrations. Instead, SAT transplantation prevented HFD-induced hepatic triacylglycerol accumulation and normalised the expression of hepatic gluconeogenic enzymes. Grafted fat displayed a significant increase in glucose uptake and unexpectedly, an induction of skeletal muscle-specific gene expression. Mice receiving subcutaneous fat also displayed a marked reduction in the plasma concentrations of several proinflammatory cytokines (TNF-α, IL-17, IL-12p70, monocyte chemoattractant protein-1 [MCP-1] and macrophage inflammatory protein-1ß [ΜIP-1ß]), compared with sham-operated mice. Plasma IL-17 and MIP-1ß concentrations were reduced from as early as 4 weeks after transplantation, and differences in plasma TNF-α and IL-17 concentrations predicted glucose tolerance and insulinaemia in the entire cohort of mice (n = 40). In contrast, mice receiving visceral fat transplants were glucose intolerant, with increased hepatic triacylglycerol content and elevated plasma IL-6 concentrations. CONCLUSIONS/INTERPRETATION: Intra-abdominal transplantation of subcutaneous fat reverses HFD-induced glucose intolerance, hepatic triacylglycerol accumulation and systemic inflammation in mice.

Reflections on implementation of a failure-point-focused outpatient parenteral antimicrobial therapy management program.

Management of outpatient parenteral antimicrobial therapy (OPAT) is complex, and incorporation of a pharmacist can improve outcomes. The creation of new clinical programs is often limited by staffing resources. We describe our collaborative program that utilized a failure-point-focused design process to optimize OPAT activities and management.

Fundamentals of viviparity: comparison of seasonal changes in the uterine epithelium of oviparous and viviparous Lerista bougainvillii (Squamata: Scincidae).

Distinct differences in epithelial response between oviparous and viviparous species of skinks led us to investigate morphological differences in the uterus of a species that exhibits bi-modal reproduction and that may indicate specialities for the different requirements of viviparity and oviparity. The uteri of females from oviparous and viviparous populations of the Australian scincid lizard, Lerista bougainvillii, are described in detail to determine whether the occurrence of uterodomes and the plasma membrane transformation, found in other viviparous species but not oviparous species, are indeed features characteristic of viviparity. Oviductal tissue was dissected at three different stages of reproduction from lizards from both populations: 1) vitellogenic, 2) gravid or pregnant, and 3) non-reproductive or quiescent. Tissue was observed using both scanning and transmission electron microscopy. Lerista bougainvillii has a simple placental morphology with simple squamous epithelium. In contrast to mammals and other viviparous skinks, L. bougainvillii does not undergo a plasma membrane transformation, but early signs of placentation in viviparous individuals are indicated by changes in the uterine surface that occur largely after embryonic stage 30. There are no obvious cellular differences between the uteri of oviparous and viviparous L. bougainvillii at the non-reproductive and vitellogenic phase of the reproductive cycle but throughout gestation/gravidity, the cellular differences that could be related to the changing functional requirements with the retention of the viviparous embryo, became apparent. A plasma membrane transformation with ensuing uterodome formation does not occur, which suggests that these more sophisticated changes are a feature of advanced placental development in reptiles.

Effect of Laparoscopic Sleeve Gastrectomy on Fasting Gastrointestinal, Pancreatic, and Adipose-Derived Hormones and on Non-Esterified Fatty Acids.

BACKGROUND: Alterations in gastrointestinal, pancreatic, and adipose hormone levels may have a greater role in weight loss than initially appreciated. The laparoscopic sleeve gastrectomy (LSG) operation is now the most frequently performed bariatric operation in many countries, but there are relatively few data regarding its molecular effects. We sought to characterize the effect of LSG on fasting plasma levels of selected hormones and on non-esterified fatty acids (NEFA), and to compare these to levels in non-obese control individuals. MATERIALS AND METHODS: The levels of nine plasma hormones were measured using a multiplex bead-based assay at baseline and at 3 months after operation in 11 obese patients undergoing LSG. NEFA levels were also measured. The levels were compared to those for 22 age- and sex-matched non-obese individuals. RESULTS: At baseline, obese patients showed significantly higher expression of C-peptide, insulin, and leptin and significantly lower ghrelin, glucose-dependent insulinotropic peptide (GIP), and resistin compared to non-obese controls (p < 0.05). LSG resulted in a reduction in BMI from 42.5 ± 6.47 kg/m2 at operation to 35.2 ± 5.14 kg/m2 at 3 months (42 % mean excess weight loss, p < 0.001). LSG led to a significant decrease in ghrelin, glucagon-like peptide-1 (GLP-1), glucagon, leptin, plasminogen activator inhibitor-1 (PAI-1), and NEFA. CONCLUSION: LSG induces marked early changes in the fasting levels of factors thought to be important regulators of obesity and metabolic health. These changes differ somewhat from the findings for operations with a malabsorptive component, suggesting that subtle differences exist in the mechanisms of weight loss between LSG and other bariatric operations.