Carolina Bravo - Academia.edu (original) (raw)

Papers by Carolina Bravo

Research paper thumbnail of Additional file 1: of Identification and functional analysis of missense mutations in the lecithin cholesterol acyltransferase gene in a Chilean patient with hypoalphalipoproteinemia

Additional file 1: of Identification and functional analysis of missense mutations in the lecithin cholesterol acyltransferase gene in a Chilean patient with hypoalphalipoproteinemia

Figure S1. LCAT genetic variants found in the proband. Sanger sequences are shown for L393 L (upp... more Figure S1. LCAT genetic variants found in the proband. Sanger sequences are shown for L393 L (upper panel), V333 M (middle panel) and M404 V (bottom panel). (JPG 77 kb)

Research paper thumbnail of PPARGC1A Gene Promoter Methylation as a Biomarker of Insulin Secretion and Sensitivity in Response to Glucose Challenges

Nutrients, 2020

Methylation in CpG sites of the PPARGC1A gene (encoding PGC1-α) has been associated with adiposit... more Methylation in CpG sites of the PPARGC1A gene (encoding PGC1-α) has been associated with adiposity, insulin secretion/sensitivity indexes and type 2 diabetes. We assessed the association between the methylation profile of the PPARGC1A gene promoter gene in leukocytes with insulin secretion/sensitivity indexes in normoglycemic women. A standard oral glucose tolerance test (OGTT) and an abbreviated version of the intravenous glucose tolerance test (IVGTT) were carried out in n = 57 Chilean nondiabetic women with measurements of plasma glucose, insulin, and C-peptide. Bisulfite-treated DNA from leukocytes was evaluated for methylation levels in six CpG sites of the proximal promoter of the PPARGC1A gene by pyrosequencing (positions -816, -783, -652, -617, -521 and -515). A strong correlation between the DNA methylation percentage of different CpG sites of the PPARGC1A promoter in leukocytes was found, suggesting an integrated epigenetic control of this region. We found a positive assoc...

Research paper thumbnail of Platelet Serotonin Levels Are Associated with Plasma Soluble Leptin Receptor Concentrations in Normoglycemic Women

Journal of Diabetes Research, 2019

Most peripheral serotonin (5-hydroxytryptamine (5HT)) is synthetized in the gut with platelets be... more Most peripheral serotonin (5-hydroxytryptamine (5HT)) is synthetized in the gut with platelets being its main circulating reservoir. 5HT is acting as a hormone in key organs to regulate glucose and lipid metabolism. However, the relation between platelet 5HT levels and traits related to glucose homeostasis and lipid metabolism in humans remains poorly explored. The objectives of this study were (a) to assess the association between platelet 5HT levels and plasma concentration of nonesterified fatty acids (NEFAs) and some adipokines including leptin and its soluble leptin receptor (sOb-R), (b) to assess the association between platelet 5HT levels and anthropometric traits and indexes of insulin secretion/sensitivity derived from oral glucose tolerance test (OGTT), and (c) to evaluate changes in platelet 5HT levels in response to OGTT. In a cross-sectional study, 59 normoglycemic women underwent a standard 2-hour OGTT. Plasma leptin, sOb-R, total and high molecular weight adiponectin,...

Research paper thumbnail of Microstructure of starch-based meals with either palm or soybean oils alter in vitro starch digestibility with no major effects on glycaemic responses

International Journal of Food Sciences and Nutrition, 2019

Glycaemic response (GR) to starch-based meals depends on their food composition and microstructur... more Glycaemic response (GR) to starch-based meals depends on their food composition and microstructure. We studied the effect of palm and soybean oils on the microstructure of a solid starch-oil-gluten matrix, on the starch gelatinisation and in vitro digestibility. Additionally, a pilot cross-over study was carried out to assess GR after eating gelatinised starch/gluten-based foods with the addition of either palm or soybean oil in 8 young non-diabetic female volunteers (ISRCTN39636850). Both types of foods generated similar starch gelatinisation temperature. Starch/gluten-based food with soybean oil had rougher microstructure compared to food with palm oil, showing a higher initial and lower final in vitro digestion. Administration of starch/gluten-based meals with either palm or soybean oils to volunteers show very similar postprandial glucose or insulin responses. In conclusion, differences in fatty acid composition changes food microstructure and in vitro starch digestibility, with no major effects on glycaemic responses in female volunteers.

Research paper thumbnail of Insulin Sensitivity Is Associated with Lipoprotein Lipase (LPL) and Catenin Delta 2 (CTNND2) DNA Methylation in Peripheral White Blood Cells in Non-Diabetic Young Women

International Journal of Molecular Sciences, 2019

Hyperglycaemia and type 2 diabetes (T2D) are associated with impaired insulin secretion and/or in... more Hyperglycaemia and type 2 diabetes (T2D) are associated with impaired insulin secretion and/or insulin action. Since few studies have addressed the relation between DNA methylation patterns with elaborated surrogates of insulin secretion/sensitivity based on the intravenous glucose tolerance test (IVGTT), the aim of this study was to evaluate the association between DNA methylation and an insulin sensitivity index based on IVGTT (calculated insulin sensitivity index (CSi)) in peripheral white blood cells from 57 non-diabetic female volunteers. The CSi and acute insulin response (AIR) indexes, as well as the disposition index (DI = CSi × AIR), were estimated from abbreviated IVGTT in 49 apparently healthy Chilean women. Methylation levels were assessed using the Illumina Infinium Human Methylation 450k BeadChip. After a statistical probe filtering, the two top CpGs whose methylation was associated with CSi were cg04615668 and cg07263235, located in the catenin delta 2 (CTNND2) and li...

Research paper thumbnail of Identification and functional analysis of missense mutations in the lecithin cholesterol acyltransferase gene in a Chilean patient with hypoalphalipoproteinemia

Lipids in Health and Disease, 2019

Background: Lecithin-cholesterol acyltransferase (LCAT) is a plasma enzyme that esterifies choles... more Background: Lecithin-cholesterol acyltransferase (LCAT) is a plasma enzyme that esterifies cholesterol in high-and low-density lipoproteins (HDL and LDL). Mutations in LCAT gene causes familial LCAT deficiency, which is characterized by very low plasma HDL-cholesterol levels (Hypoalphalipoproteinemia), corneal opacity and anemia, among other lipid-related traits. Our aim is to evaluate clinical/biochemical features of a Chilean family with a proband showing clinical signs of familial LCAT deficiency, as well as to identify and assess the functional effects of LCAT mutations. Methods: An adult female proband with hypoalphalipoproteinemia, corneal opacity and mild anemia, as well as her first-degree relatives, were recruited for clinical, biochemical, genetic, in-silico and in-vitro LCAT analysis. Sequencing of exons and intron-exon boundaries was performed to identify mutations. Site-directed mutagenesis was carried out to generate plasmids containing cDNA with wild type or mutant sequences. Such expression vectors were transfected to HEK-239 T cells to asses the effect of LCAT variants in expression, synthesis, secretion and enzyme activity. In-silico prediction analysis and molecular modeling was also used to evaluate the effect of LCAT variants.

Research paper thumbnail of Leptin/Adiponectin Ratios Using Either Total Or High-Molecular-Weight Adiponectin as Biomarkers of Systemic Insulin Sensitivity in Normoglycemic Women

Journal of diabetes research, 2017

Plasma leptin/adiponectin ratio (LAR) is negatively associated with insulin sensitivity indexes. ... more Plasma leptin/adiponectin ratio (LAR) is negatively associated with insulin sensitivity indexes. High-molecular-weight adiponectin (HMWA) was proposed as the most biologically active form of this insulin-sensitizing adipokine. There are no studies assessing the relative merits of leptin/HMWA ratio over LAR as a biomarker of systemic insulin sensitivity. A standard 2-hour oral glucose tolerance test (OGTT; 75 g of glucose) and a short minimal-model intravenous glucose tolerance test (IVGTT; 0.3 g/kg body weight) were performed in 58 Chilean normoglycemic women (age: 27 ± 6.3 years, BMI 23.6 ± 3.2 kg/m(2)). LAR was negatively associated with HOMA-S (r = -0.49; p < 0.0001), Matsuda-ISICOMP (r = -0.54; p < 0.0001), and the calculated sensitivity index (CSi) derived from IVGTT (r = -0.38; p = 0.007). In comparison to LAR, leptin/HMWA ratio did not increase neither the linear fit (r(2)) nor the magnitude of association with insulin sensitivity indexes (slope of multiple linear regre...

Research paper thumbnail of Additional file 1: of Identification and functional analysis of missense mutations in the lecithin cholesterol acyltransferase gene in a Chilean patient with hypoalphalipoproteinemia

Additional file 1: of Identification and functional analysis of missense mutations in the lecithin cholesterol acyltransferase gene in a Chilean patient with hypoalphalipoproteinemia

Figure S1. LCAT genetic variants found in the proband. Sanger sequences are shown for L393 L (upp... more Figure S1. LCAT genetic variants found in the proband. Sanger sequences are shown for L393 L (upper panel), V333 M (middle panel) and M404 V (bottom panel). (JPG 77 kb)

Research paper thumbnail of PPARGC1A Gene Promoter Methylation as a Biomarker of Insulin Secretion and Sensitivity in Response to Glucose Challenges

Nutrients, 2020

Methylation in CpG sites of the PPARGC1A gene (encoding PGC1-α) has been associated with adiposit... more Methylation in CpG sites of the PPARGC1A gene (encoding PGC1-α) has been associated with adiposity, insulin secretion/sensitivity indexes and type 2 diabetes. We assessed the association between the methylation profile of the PPARGC1A gene promoter gene in leukocytes with insulin secretion/sensitivity indexes in normoglycemic women. A standard oral glucose tolerance test (OGTT) and an abbreviated version of the intravenous glucose tolerance test (IVGTT) were carried out in n = 57 Chilean nondiabetic women with measurements of plasma glucose, insulin, and C-peptide. Bisulfite-treated DNA from leukocytes was evaluated for methylation levels in six CpG sites of the proximal promoter of the PPARGC1A gene by pyrosequencing (positions -816, -783, -652, -617, -521 and -515). A strong correlation between the DNA methylation percentage of different CpG sites of the PPARGC1A promoter in leukocytes was found, suggesting an integrated epigenetic control of this region. We found a positive assoc...

Research paper thumbnail of Platelet Serotonin Levels Are Associated with Plasma Soluble Leptin Receptor Concentrations in Normoglycemic Women

Journal of Diabetes Research, 2019

Most peripheral serotonin (5-hydroxytryptamine (5HT)) is synthetized in the gut with platelets be... more Most peripheral serotonin (5-hydroxytryptamine (5HT)) is synthetized in the gut with platelets being its main circulating reservoir. 5HT is acting as a hormone in key organs to regulate glucose and lipid metabolism. However, the relation between platelet 5HT levels and traits related to glucose homeostasis and lipid metabolism in humans remains poorly explored. The objectives of this study were (a) to assess the association between platelet 5HT levels and plasma concentration of nonesterified fatty acids (NEFAs) and some adipokines including leptin and its soluble leptin receptor (sOb-R), (b) to assess the association between platelet 5HT levels and anthropometric traits and indexes of insulin secretion/sensitivity derived from oral glucose tolerance test (OGTT), and (c) to evaluate changes in platelet 5HT levels in response to OGTT. In a cross-sectional study, 59 normoglycemic women underwent a standard 2-hour OGTT. Plasma leptin, sOb-R, total and high molecular weight adiponectin,...

Research paper thumbnail of Microstructure of starch-based meals with either palm or soybean oils alter in vitro starch digestibility with no major effects on glycaemic responses

International Journal of Food Sciences and Nutrition, 2019

Glycaemic response (GR) to starch-based meals depends on their food composition and microstructur... more Glycaemic response (GR) to starch-based meals depends on their food composition and microstructure. We studied the effect of palm and soybean oils on the microstructure of a solid starch-oil-gluten matrix, on the starch gelatinisation and in vitro digestibility. Additionally, a pilot cross-over study was carried out to assess GR after eating gelatinised starch/gluten-based foods with the addition of either palm or soybean oil in 8 young non-diabetic female volunteers (ISRCTN39636850). Both types of foods generated similar starch gelatinisation temperature. Starch/gluten-based food with soybean oil had rougher microstructure compared to food with palm oil, showing a higher initial and lower final in vitro digestion. Administration of starch/gluten-based meals with either palm or soybean oils to volunteers show very similar postprandial glucose or insulin responses. In conclusion, differences in fatty acid composition changes food microstructure and in vitro starch digestibility, with no major effects on glycaemic responses in female volunteers.

Research paper thumbnail of Insulin Sensitivity Is Associated with Lipoprotein Lipase (LPL) and Catenin Delta 2 (CTNND2) DNA Methylation in Peripheral White Blood Cells in Non-Diabetic Young Women

International Journal of Molecular Sciences, 2019

Hyperglycaemia and type 2 diabetes (T2D) are associated with impaired insulin secretion and/or in... more Hyperglycaemia and type 2 diabetes (T2D) are associated with impaired insulin secretion and/or insulin action. Since few studies have addressed the relation between DNA methylation patterns with elaborated surrogates of insulin secretion/sensitivity based on the intravenous glucose tolerance test (IVGTT), the aim of this study was to evaluate the association between DNA methylation and an insulin sensitivity index based on IVGTT (calculated insulin sensitivity index (CSi)) in peripheral white blood cells from 57 non-diabetic female volunteers. The CSi and acute insulin response (AIR) indexes, as well as the disposition index (DI = CSi × AIR), were estimated from abbreviated IVGTT in 49 apparently healthy Chilean women. Methylation levels were assessed using the Illumina Infinium Human Methylation 450k BeadChip. After a statistical probe filtering, the two top CpGs whose methylation was associated with CSi were cg04615668 and cg07263235, located in the catenin delta 2 (CTNND2) and li...

Research paper thumbnail of Identification and functional analysis of missense mutations in the lecithin cholesterol acyltransferase gene in a Chilean patient with hypoalphalipoproteinemia

Lipids in Health and Disease, 2019

Background: Lecithin-cholesterol acyltransferase (LCAT) is a plasma enzyme that esterifies choles... more Background: Lecithin-cholesterol acyltransferase (LCAT) is a plasma enzyme that esterifies cholesterol in high-and low-density lipoproteins (HDL and LDL). Mutations in LCAT gene causes familial LCAT deficiency, which is characterized by very low plasma HDL-cholesterol levels (Hypoalphalipoproteinemia), corneal opacity and anemia, among other lipid-related traits. Our aim is to evaluate clinical/biochemical features of a Chilean family with a proband showing clinical signs of familial LCAT deficiency, as well as to identify and assess the functional effects of LCAT mutations. Methods: An adult female proband with hypoalphalipoproteinemia, corneal opacity and mild anemia, as well as her first-degree relatives, were recruited for clinical, biochemical, genetic, in-silico and in-vitro LCAT analysis. Sequencing of exons and intron-exon boundaries was performed to identify mutations. Site-directed mutagenesis was carried out to generate plasmids containing cDNA with wild type or mutant sequences. Such expression vectors were transfected to HEK-239 T cells to asses the effect of LCAT variants in expression, synthesis, secretion and enzyme activity. In-silico prediction analysis and molecular modeling was also used to evaluate the effect of LCAT variants.

Research paper thumbnail of Leptin/Adiponectin Ratios Using Either Total Or High-Molecular-Weight Adiponectin as Biomarkers of Systemic Insulin Sensitivity in Normoglycemic Women

Journal of diabetes research, 2017

Plasma leptin/adiponectin ratio (LAR) is negatively associated with insulin sensitivity indexes. ... more Plasma leptin/adiponectin ratio (LAR) is negatively associated with insulin sensitivity indexes. High-molecular-weight adiponectin (HMWA) was proposed as the most biologically active form of this insulin-sensitizing adipokine. There are no studies assessing the relative merits of leptin/HMWA ratio over LAR as a biomarker of systemic insulin sensitivity. A standard 2-hour oral glucose tolerance test (OGTT; 75 g of glucose) and a short minimal-model intravenous glucose tolerance test (IVGTT; 0.3 g/kg body weight) were performed in 58 Chilean normoglycemic women (age: 27 ± 6.3 years, BMI 23.6 ± 3.2 kg/m(2)). LAR was negatively associated with HOMA-S (r = -0.49; p < 0.0001), Matsuda-ISICOMP (r = -0.54; p < 0.0001), and the calculated sensitivity index (CSi) derived from IVGTT (r = -0.38; p = 0.007). In comparison to LAR, leptin/HMWA ratio did not increase neither the linear fit (r(2)) nor the magnitude of association with insulin sensitivity indexes (slope of multiple linear regre...