Cardiometabolic plasticity and skeletal muscle protein expression in Hispanic and non-Hispanic whites in response to a short-term diet and exercise intervention
Date
2009
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Abstract
The prevalence rates for type 2 diabetes (T2D) and the metabolic syndrome (MetS) have steadily increased to epidemic proportions over the past few decades, with disproportionately high rates of these health problems in Hispanics. The largest minority group in the United States is Hispanics, with Mexican Americans (MA) comprising the largest and fastest growing portion of the US Hispanic population. Insulin resistance is more prevalent in the MA population compared to other ethnic groups, and appears to precede many of the metabolic abnormalities involved in the progression toward T2D and MetS. Insulin resistance and many factors present in the MetS have been shown to improve following an increase in physical activity and consumption of diets low in saturated fatty acids and high in fiber. The overall objective of this project was to determine the combined effects of an increase in exercise combined with dietary lipid and carbohydrate modification on insulin sensitivity and blood lipids, and to determine if differences in expression of skeletal muscle proteins exist in non-obese, non-diabetic sedentary MA and NHW adults.
In Arm 1 of the study, we determined whether differences in insulin sensitivity persist following a short-term diet and exercise intervention between young, sedentary, non-obese, non-diabetic subjects (20 NHW: 11F, 9M, age=23.0 y, BMI=25.5; 17 MA: 13F, 4M, age=22.7, BMI=25.4). In addition, we determined whether or not differences in insulin sensitivity led to greater dyslipidemia in MA compared to NHW and whether or not these two ethnic groups responded similarly to the same lifestyle intervention. Both MA and NHW had significant improvements in insulin sensitivity, determined by total insulin area under the curve (AUC) during an intravenous glucose tolerance test, following the intervention, suggesting that MA exhibit similar cardiometabolic plasticity as NHW. However, significant differences in insulin sensitivity were observed both before and following the short-term diet and exercise intervention in MA compared to NHW, and the disparity in insulin sensitivity remained. Despite differences in insulin sensitivity, we observed no differences in blood lipids (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, small dense LDL particles, and non-esterified fatty acids) pre or post intervention between ethnicities. Even though both ethnic groups exhibited normal blood lipids at the outset of the study, both ethnic groups had significant decreases in total cholesterol, LDL-cholesterol, triglycerides, and small dense LDL particles following the short-term intervention. Our results suggest that MA respond to a short-term lifestyle intervention in a similar manner as NHW, although the ethnic disparity in insulin sensitivity is not attenuated.
In Arm 2 of our study, we utilized a proteomics approach to examine expression of skeletal muscle proteins in a subset of 3 MA and 3 NHW subjects in order to provide potential targets for further analysis on the entire study cohort. We found differences in expression of two mitochondrial proteins, carnitine palmitoyltransferase 1A isoform 2 (CPT-1) and mitochondrial ATP synthase Fl complex beta subunit (ATP synthase). ATP synthase was 3-fold higher in NHW (NHW= 188.4 ± 10.2 and MA = 62.7 ± 28.4), while CPT-1 was 1.7 times higher in NHW compared to MA (NHW= 190.4 ± 1.3 vs MA = 109.3 ± 12.6). Western blot analysis of skeletal muscle ATP synthase in 11 MA (3 males, 8 females) and 10 NHW (3 males, 7 females) revealed no differences in protein abundance between ethnic groups or following the insulin-sensitizing diet and exercise intervention. Therefore, despite the findings from the proteomic analysis, there is no evidence that ATP synthase differs in skeletal muscle of MA compared to NHW. CPT-1 analysis has not yet been completed due to difficulties in measuring CPT-1 in skeletal muscle. Further work to identify possible differences in skeletal muscle proteins and their activation between MA and NHW is warranted.
In Arm 1 of the study, we determined whether differences in insulin sensitivity persist following a short-term diet and exercise intervention between young, sedentary, non-obese, non-diabetic subjects (20 NHW: 11F, 9M, age=23.0 y, BMI=25.5; 17 MA: 13F, 4M, age=22.7, BMI=25.4). In addition, we determined whether or not differences in insulin sensitivity led to greater dyslipidemia in MA compared to NHW and whether or not these two ethnic groups responded similarly to the same lifestyle intervention. Both MA and NHW had significant improvements in insulin sensitivity, determined by total insulin area under the curve (AUC) during an intravenous glucose tolerance test, following the intervention, suggesting that MA exhibit similar cardiometabolic plasticity as NHW. However, significant differences in insulin sensitivity were observed both before and following the short-term diet and exercise intervention in MA compared to NHW, and the disparity in insulin sensitivity remained. Despite differences in insulin sensitivity, we observed no differences in blood lipids (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, small dense LDL particles, and non-esterified fatty acids) pre or post intervention between ethnicities. Even though both ethnic groups exhibited normal blood lipids at the outset of the study, both ethnic groups had significant decreases in total cholesterol, LDL-cholesterol, triglycerides, and small dense LDL particles following the short-term intervention. Our results suggest that MA respond to a short-term lifestyle intervention in a similar manner as NHW, although the ethnic disparity in insulin sensitivity is not attenuated.
In Arm 2 of our study, we utilized a proteomics approach to examine expression of skeletal muscle proteins in a subset of 3 MA and 3 NHW subjects in order to provide potential targets for further analysis on the entire study cohort. We found differences in expression of two mitochondrial proteins, carnitine palmitoyltransferase 1A isoform 2 (CPT-1) and mitochondrial ATP synthase Fl complex beta subunit (ATP synthase). ATP synthase was 3-fold higher in NHW (NHW= 188.4 ± 10.2 and MA = 62.7 ± 28.4), while CPT-1 was 1.7 times higher in NHW compared to MA (NHW= 190.4 ± 1.3 vs MA = 109.3 ± 12.6). Western blot analysis of skeletal muscle ATP synthase in 11 MA (3 males, 8 females) and 10 NHW (3 males, 7 females) revealed no differences in protein abundance between ethnic groups or following the insulin-sensitizing diet and exercise intervention. Therefore, despite the findings from the proteomic analysis, there is no evidence that ATP synthase differs in skeletal muscle of MA compared to NHW. CPT-1 analysis has not yet been completed due to difficulties in measuring CPT-1 in skeletal muscle. Further work to identify possible differences in skeletal muscle proteins and their activation between MA and NHW is warranted.
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cardiometabolic plasticity
diabetes
exercise intervention
metabolic syndrome
skeletal muscle
nutrition
physiology