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Subcutaneous fat transplantation alleviates diet-induced glucose intolerance and inflammation in mice
Annual Scientific Meeting website provides important information and individually tailored applications for healthy eating and physical activity to achieve a healthy weight. Tactical advertising promotes the campaign’s advocacy priorities. The impact of Phase II of the campaign was assessed using computer assisted telephone surveys (CATI) of a cohort of 1500 adults between August 2013 and April 2014. Results: Responses from the junk food and drink industries, the media industry and international and national stakeholders advocating for the Campaign to be run outside Western Australia will be presented together with process evaluation data from the Campaign. Conclusion: The LiveLighter campaign has demonstrated that hard hitting public education campaigns can be successful in raising awareness, especially among overweight and obese adults. The Campaign has achieved important traction for the issue of obesity and the development of chronic disease in Western Australia. Consequently, the LiveLighter campaign is now being conducted in Victoria and the ACT and is generating interest internationally. http://dx.doi.org/10.1016/j.orcp.2014.10.181
99 25 Subcutaneous fat transplantation alleviates diet-induced glucose intolerance and inflammation in mice Samantha L. Hocking 1,2,∗ , Rebecca L. Stewart 1 , Amanda E. Brandon 1 , Eurwin Suryana 1 , Emily M. Baldwin 1 , Ganesh A. Kolumam 3 , Michael Medynskyj 4,5 , Sinead P. Blaber 4,5 , Elisabeth Karsten 4,5 , Benjamin R. Herbert 4,5 , Gregory J. Cooney 1,6 , Michael M. Swarbrick 1,7 1 Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW, Australia 2 Endocrinology, Royal North Shore Hospital, St. Leonard’s, NSW, Australia 3 Tumor Biology and Angiogenesis, Genentech, Inc, South San Francisco, California, USA 4 Regeneus, Ltd, Pymble, NSW, Australia 5 Department of Chemistry and Biomolecular Science, Macquarie University, Sydney, NSW, Australia 6 St Vincent’s Clinical School, University of New South Wales Australia, Darlinghurst, NSW, Australia 7 School of Medical Sciences, University of New South Wales, Kengington, NSW, Australia
Background: Adipose tissue distribution is a major determinant of mortality and morbidity in obesity. In mice, intra-abdominal transplantation of subcutaneous adipose tissue protects against glucose intolerance and insulin resistance, but the underlying mechanisms are not well understood. Methods: We investigated changes in adipokines, tissue-specific glucose uptake and systemic inflammation in male C57BL6/J mice implanted intraabdominally with either inguinal (subcutaneous) or epididymal (visceral) adipose tissue and fed a high-fat diet (HFD) for up to 17 weeks. Gene expression in grafted and endogenous adipose tissues was examined by microarray, and the expression of 84 fatty liver-associated genes involved were measured using PCR arrays (Qiagen). Plasma cytokine concentrations were measured using Bio-plex Pro assays (Bio-Rad).
100 Results: Glucose tolerance was significantly improved in mice receiving subcutaneous adipose tissue from 6 weeks after transplantation, and was observed independently of body weight, skeletal muscle glucose uptake, and plasma leptin and adiponectin concentrations. In these mice, high-fat diet-induced increases in plasma concentrations of several pro-inflammatory cytokines (tumour necrosis factor-␣ (TNF-␣), interleukin17 (IL-17), IL-12p70, monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1) were markedly suppressed, relative to sham-operated mice. Notably, plasma concentrations of IL-17 and MIP-1 were reduced from as early as 4 weeks after transplantation. Of these cytokines, differences in plasma TNF␣ and IL-17 concentrations significantly predicted subsequent improvements in glucose tolerance and insulinaemia in the entire group of mice (n = 40). Grafted fat displayed a significant increase in glucose uptake and unexpectedly, a marked induction of skeletal muscle gene expression. Consistent with improved glucose tolerance, hepatic triglyceride accumulation was significantly attenuated in mice receiving subcutaneous fat transplants. In contrast, mice receiving additional intra-abdominal adipose tissue displayed the greatest degree of hepatic triglyceride accumulation, and uniquely elevated plasma IL-6 concentrations. Conclusions: Intra-abdominal transplantation of subcutaneous fat has reproducible beneficial effects on glucose tolerance and systemic inflammation. Future studies will be required to identify the cell type(s) responsible for these effects, and potential sites for therapeutic intervention. http://dx.doi.org/10.1016/j.orcp.2014.10.182
M. Pickford 68 Human gastro-oesophageal adipose tissue (GO fat): A depot enriched in thermogenic beige/brige adipocytes Frank L.S. Kyang 1,∗ , Rebecca L. Stewart 2 , Brielle Wood 2,3 , Evgenii Borodachev 1 , Michael M. Swarbrick 2,4 , Reginald V. Lord 1,3 1 St.
Vincent’s Institute for Applied Medical Research, Darlinghurst, NSW, Australia 2 Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW, Australia 3 University of Notre Dame Australia, Darlinghurst, NSW, Australia 4 School of Medical Sciences, University of New South Wales, Kengington, NSW, Australia
Background: Recently, thermogenic beige/brite adipocytes with potential anti-obesity effects have been isolated from rodent white adipose tissue. Beige/brite adipocytes are characterised by inducible uncoupling protein-1 (UCP1) expression, and by the cell surface markers TMEM26 and CD137 (Wu J, et al. Cell; 2012). In humans, beige/brite cells have been identified in several human adipose depots, including supraclavicular, mediastinal, retroperitoneal and intra-abdominal fat. These cells were proposed to express the marker CITED1 (Sharp LZ, et al. PLoS ONE; 2013). We aimed to identify beige/brite cells in human fat, to examine their relationship with obesity/diabetes and to establish an in vitro model. Subjects and methods: Adipose tissues (omental, gastro-oesophageal (GO fat) and abdominal subcutaneous) were obtained from 32 subjects undergoing routine abdominal surgery at SVH, Darlinghurst. This included 8 non-obese (3M/5F, BMI 21.7—27.1 kg/m2 ), 11 obese (2M/9F, BMI 33.9—39.9 kg/m2 ) and 13 severely obese (6M/7F, BMI 41.3—57.2 kg/m2 ) subjects. Tissues were fixed for UCP1 immunohistochemistry, and mRNA expression of thermogenic genes (UCP1, PPARGC1A) and beige/brite identity (PRDM16, TMEM26, CD137, CITED1 and TBX15) was measured by RT-PCR. Results: Half of all GO fat samples, and 44% of omental samples had detectable multilocular UCP1 + adipocytes. Beige/brite adipocyte prevalence was not associated with BMI or diabetes. GO fat tended to express the highest levels of mRNAs encoding UCP1 (1.90-fold vs. omental fat, P = 0.13) and PPARGC1A (1.99-fold vs omen-
99 25 Subcutaneous fat transplantation alleviates diet-induced glucose intolerance and inflammation in mice Samantha L. Hocking 1,2,∗ , Rebecca L. Stewart 1 , Amanda E. Brandon 1 , Eurwin Suryana 1 , Emily M. Baldwin 1 , Ganesh A. Kolumam 3 , Michael Medynskyj 4,5 , Sinead P. Blaber 4,5 , Elisabeth Karsten 4,5 , Benjamin R. Herbert 4,5 , Gregory J. Cooney 1,6 , Michael M. Swarbrick 1,7 1 Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW, Australia 2 Endocrinology, Royal North Shore Hospital, St. Leonard’s, NSW, Australia 3 Tumor Biology and Angiogenesis, Genentech, Inc, South San Francisco, California, USA 4 Regeneus, Ltd, Pymble, NSW, Australia 5 Department of Chemistry and Biomolecular Science, Macquarie University, Sydney, NSW, Australia 6 St Vincent’s Clinical School, University of New South Wales Australia, Darlinghurst, NSW, Australia 7 School of Medical Sciences, University of New South Wales, Kengington, NSW, Australia
Background: Adipose tissue distribution is a major determinant of mortality and morbidity in obesity. In mice, intra-abdominal transplantation of subcutaneous adipose tissue protects against glucose intolerance and insulin resistance, but the underlying mechanisms are not well understood. Methods: We investigated changes in adipokines, tissue-specific glucose uptake and systemic inflammation in male C57BL6/J mice implanted intraabdominally with either inguinal (subcutaneous) or epididymal (visceral) adipose tissue and fed a high-fat diet (HFD) for up to 17 weeks. Gene expression in grafted and endogenous adipose tissues was examined by microarray, and the expression of 84 fatty liver-associated genes involved were measured using PCR arrays (Qiagen). Plasma cytokine concentrations were measured using Bio-plex Pro assays (Bio-Rad).
100 Results: Glucose tolerance was significantly improved in mice receiving subcutaneous adipose tissue from 6 weeks after transplantation, and was observed independently of body weight, skeletal muscle glucose uptake, and plasma leptin and adiponectin concentrations. In these mice, high-fat diet-induced increases in plasma concentrations of several pro-inflammatory cytokines (tumour necrosis factor-␣ (TNF-␣), interleukin17 (IL-17), IL-12p70, monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1) were markedly suppressed, relative to sham-operated mice. Notably, plasma concentrations of IL-17 and MIP-1 were reduced from as early as 4 weeks after transplantation. Of these cytokines, differences in plasma TNF␣ and IL-17 concentrations significantly predicted subsequent improvements in glucose tolerance and insulinaemia in the entire group of mice (n = 40). Grafted fat displayed a significant increase in glucose uptake and unexpectedly, a marked induction of skeletal muscle gene expression. Consistent with improved glucose tolerance, hepatic triglyceride accumulation was significantly attenuated in mice receiving subcutaneous fat transplants. In contrast, mice receiving additional intra-abdominal adipose tissue displayed the greatest degree of hepatic triglyceride accumulation, and uniquely elevated plasma IL-6 concentrations. Conclusions: Intra-abdominal transplantation of subcutaneous fat has reproducible beneficial effects on glucose tolerance and systemic inflammation. Future studies will be required to identify the cell type(s) responsible for these effects, and potential sites for therapeutic intervention. http://dx.doi.org/10.1016/j.orcp.2014.10.182
M. Pickford 68 Human gastro-oesophageal adipose tissue (GO fat): A depot enriched in thermogenic beige/brige adipocytes Frank L.S. Kyang 1,∗ , Rebecca L. Stewart 2 , Brielle Wood 2,3 , Evgenii Borodachev 1 , Michael M. Swarbrick 2,4 , Reginald V. Lord 1,3 1 St.
Vincent’s Institute for Applied Medical Research, Darlinghurst, NSW, Australia 2 Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW, Australia 3 University of Notre Dame Australia, Darlinghurst, NSW, Australia 4 School of Medical Sciences, University of New South Wales, Kengington, NSW, Australia
Background: Recently, thermogenic beige/brite adipocytes with potential anti-obesity effects have been isolated from rodent white adipose tissue. Beige/brite adipocytes are characterised by inducible uncoupling protein-1 (UCP1) expression, and by the cell surface markers TMEM26 and CD137 (Wu J, et al. Cell; 2012). In humans, beige/brite cells have been identified in several human adipose depots, including supraclavicular, mediastinal, retroperitoneal and intra-abdominal fat. These cells were proposed to express the marker CITED1 (Sharp LZ, et al. PLoS ONE; 2013). We aimed to identify beige/brite cells in human fat, to examine their relationship with obesity/diabetes and to establish an in vitro model. Subjects and methods: Adipose tissues (omental, gastro-oesophageal (GO fat) and abdominal subcutaneous) were obtained from 32 subjects undergoing routine abdominal surgery at SVH, Darlinghurst. This included 8 non-obese (3M/5F, BMI 21.7—27.1 kg/m2 ), 11 obese (2M/9F, BMI 33.9—39.9 kg/m2 ) and 13 severely obese (6M/7F, BMI 41.3—57.2 kg/m2 ) subjects. Tissues were fixed for UCP1 immunohistochemistry, and mRNA expression of thermogenic genes (UCP1, PPARGC1A) and beige/brite identity (PRDM16, TMEM26, CD137, CITED1 and TBX15) was measured by RT-PCR. Results: Half of all GO fat samples, and 44% of omental samples had detectable multilocular UCP1 + adipocytes. Beige/brite adipocyte prevalence was not associated with BMI or diabetes. GO fat tended to express the highest levels of mRNAs encoding UCP1 (1.90-fold vs. omental fat, P = 0.13) and PPARGC1A (1.99-fold vs omen-