S Kitajima1, M Morimoto2, E Liu2, T Koike3, Y Higaki4, Y Taura5, K Mamba6, K Itamoto5, T Watanabe7, K Tsutsumi8, N Yamada9, J Fan3. 1. Analytical Research Center for Experimental Sciences, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan. kitajims@med.saga-u.ac.jp. 2. Analytical Research Center for Experimental Sciences, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan. 3. Cardiovascular Disease Laboratory, Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Japan. 4. Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga, Japan. 5. Department of Veterinary Surgery, Veterinary Clinical Science, Yamaguchi University, Yamaguchi, Japan. 6. United Graduate School of Veterinary Sciences, Yamaguchi University, Yamaguchi, Japan. 7. Saga University, Saga, Japan. 8. Otsuka Pharmaceutical Factory, Tokushima, Japan. 9. Department of Metabolism and Endocrinology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.
Abstract
AIMS/HYPOTHESIS: Dysfunctions of lipoprotein lipase (LPL) have been found to be associated with dyslipidaemias, atherosclerosis, obesity and insulin resistance. There are two conflicting hypotheses regarding the roles of LPL in glucose metabolism and insulin resistance. Whether systemically increased LPL activity would be beneficial or detrimental to insulin sensitivity is yet to be resolved. To address this issue, we studied transgenic rabbits overexpressing human LPL transgene. METHODS: LPL transgenic and control rabbits were fed a 10% high-fat diet (HFD) for 16 weeks. To evaluate glucose metabolism, we compared plasma levels of glucose and insulin in transgenic rabbits with control rabbits and performed an intravenous glucose tolerance test. In addition, we measured adipose tissue accumulation in HFD-fed rabbits. RESULTS: Increased LPL activity in transgenic rabbits resulted in a significant reduction of plasma triglycerides and non-esterified fatty acids, but not in basal levels of glucose and insulin. HFD feeding induced an elevation of plasma glucose levels accompanied by hyperinsulinaemia in control rabbits, but was significantly inhibited in transgenic rabbits. The intravenous glucose tolerance test showed that transgenic rabbits had faster glucose clearance associated with lower levels of insulin secretion than control rabbits. In addition, there was a significant reduction of body adipose tissue in transgenic rabbits compared with in control rabbits fed an HFD. Scanning electron microscopic examination revealed that adipocytes in transgenic rabbits were predominately small cells. CONCLUSIONS/ INTERPRETATION: Our results showed that systemically increased LPL activity improves insulin resistance and reduces adipose accumulation in transgenic rabbits, indicating that systemic elevation of LPL may have potential benefits for the treatment of insulin resistance and obesity.
AIMS/HYPOTHESIS: Dysfunctions of lipoprotein lipase (LPL) have been found to be associated with dyslipidaemias, atherosclerosis, obesity and insulin resistance. There are two conflicting hypotheses regarding the roles of LPL in glucose metabolism and insulin resistance. Whether systemically increased LPL activity would be beneficial or detrimental to insulin sensitivity is yet to be resolved. To address this issue, we studied transgenic rabbits overexpressing humanLPL transgene. METHODS:LPL transgenic and control rabbits were fed a 10% high-fat diet (HFD) for 16 weeks. To evaluate glucose metabolism, we compared plasma levels of glucose and insulin in transgenic rabbits with control rabbits and performed an intravenous glucose tolerance test. In addition, we measured adipose tissue accumulation in HFD-fed rabbits. RESULTS: Increased LPL activity in transgenic rabbits resulted in a significant reduction of plasma triglycerides and non-esterified fatty acids, but not in basal levels of glucose and insulin. HFD feeding induced an elevation of plasma glucose levels accompanied by hyperinsulinaemia in control rabbits, but was significantly inhibited in transgenic rabbits. The intravenous glucose tolerance test showed that transgenic rabbits had faster glucose clearance associated with lower levels of insulin secretion than control rabbits. In addition, there was a significant reduction of body adipose tissue in transgenic rabbits compared with in control rabbits fed an HFD. Scanning electron microscopic examination revealed that adipocytes in transgenic rabbits were predominately small cells. CONCLUSIONS/ INTERPRETATION: Our results showed that systemically increased LPL activity improves insulin resistance and reduces adipose accumulation in transgenic rabbits, indicating that systemic elevation of LPL may have potential benefits for the treatment of insulin resistance and obesity.
Authors: M Kusunoki; T Hara; K Tsutsumi; T Nakamura; T Miyata; F Sakakibara; S Sakamoto; H Ogawa; Y Nakaya; L H Storlien Journal: Diabetologia Date: 2000-07 Impact factor: 10.122
Authors: G Mingrone; F L Henriksen; A V Greco; L N Krogh; E Capristo; A Gastaldelli; M Castagneto; E Ferrannini; G Gasbarrini; H Beck-Nielsen Journal: Diabetes Date: 1999-06 Impact factor: 9.461
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Authors: Ira J Smith; Kim M Huffman; Michael T Durheim; Brian D Duscha; William E Kraus Journal: Physiol Genomics Date: 2008-11-25 Impact factor: 3.107