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1.
Gastroenterology ; 150(1): 79-81.e2, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26376348

RESUMO

Weight gain is associated with an increase in intrahepatic triglycerides (IHTGs), and is the primary cause of nonalcoholic fatty liver disease in obese individuals. We combined imaging and stable isotope tracer techniques to evaluate the physiologic mechanisms of weight gain-induced steatosis in 27 obese people. Weight gain appeared to increase IHTG content by generating an imbalance between hepatic fatty acid availability and disposal, and resulted in increased hepatic de novo lipogenesis, decreased intrahepatic fatty acid oxidation, and inadequate increases in IHTG export via very low-density lipoprotein secretion. ClinicalTrials.gov ID NCT01184170.


Assuntos
Composição Corporal , Fígado Gorduroso/metabolismo , Metabolismo dos Lipídeos/fisiologia , Obesidade/metabolismo , Aumento de Peso/fisiologia , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Ácidos Graxos/metabolismo , Fígado Gorduroso/diagnóstico por imagem , Feminino , Humanos , Lipoproteínas VLDL/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Cintilografia , Valores de Referência , Medição de Risco
2.
Gastroenterology ; 145(2): 366-74.e1-3, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23597726

RESUMO

BACKGROUND & AIMS: An increased number of macrophages in adipose tissue is associated with insulin resistance and metabolic dysfunction in obese people. However, little is known about other immune cells in adipose tissue from obese people, and whether they contribute to insulin resistance. We investigated the characteristics of T cells in adipose tissue from metabolically abnormal insulin-resistant obese (MAO) subjects, metabolically normal insulin-sensitive obese (MNO) subjects, and lean subjects. Insulin sensitivity was determined by using the hyperinsulinemic euglycemic clamp procedure. METHODS: We assessed plasma cytokine concentrations and subcutaneous adipose tissue CD4(+) T-cell populations in 9 lean, 12 MNO, and 13 MAO subjects. Skeletal muscle and liver samples were collected from 19 additional obese patients undergoing bariatric surgery to determine the presence of selected cytokine receptors. RESULTS: Adipose tissue from MAO subjects had 3- to 10-fold increases in numbers of CD4(+) T cells that produce interleukin (IL)-22 and IL-17 (a T-helper [Th] 17 and Th22 phenotype) compared with MNO and lean subjects. MAO subjects also had increased plasma concentrations of IL-22 and IL-6. Receptors for IL-17 and IL-22 were expressed in human liver and skeletal muscle samples. IL-17 and IL-22 inhibited uptake of glucose in skeletal muscle isolated from rats and reduced insulin sensitivity in cultured human hepatocytes. CONCLUSIONS: Adipose tissue from MAO individuals contains increased numbers of Th17 and Th22 cells, which produce cytokines that cause metabolic dysfunction in liver and muscle in vitro. Additional studies are needed to determine whether these alterations in adipose tissue T cells contribute to the pathogenesis of insulin resistance in obese people.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Citocinas/imunologia , Resistência à Insulina/imunologia , Obesidade/imunologia , Gordura Subcutânea/imunologia , Adulto , Animais , Índice de Massa Corporal , Linfócitos T CD4-Positivos/metabolismo , Estudos de Casos e Controles , Feminino , Glucose/metabolismo , Técnica Clamp de Glucose , Hepatócitos/efeitos dos fármacos , Humanos , Interleucina-17/metabolismo , Interleucina-17/farmacologia , Interleucina-6/sangue , Interleucinas/sangue , Interleucinas/metabolismo , Interleucinas/farmacologia , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Ratos , Receptores de Interleucina/metabolismo , Receptores de Interleucina-17/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Interleucina 22
3.
J Hum Lact ; 36(4): 791-794, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31895601

RESUMO

INTRODUCTION: Breastfeeding offers the optimal feeding option for newborns in terms of nutritional content and reinforces mother-infant bonding. As a physiological process intrinsically linked to parturition, breastfeeding is no longer reserved for puerperal mothers. Progress in understanding the intricacies of lactogenesis and breastfeeding has further paved the way for artificially induced lactation in recent years. MAIN ISSUES: We describe the case of a mother through surrogacy with XY karyotype and complete androgen insensitivity syndrome who wished to breastfeed her child. MANAGEMENT: Through a combination of estrogen therapy, galactagogues, and mechanical breast stimulation she was able to partially breastfeed her child for one month. CONCLUSION: This case further shifts the concept that breastfeeding is a physiological process confined to only puerperal mothers and offers an opportunity to a wider group of nontraditional mothers to take part in the unique experience of breastfeeding.


Assuntos
Síndrome de Resistência a Andrógenos/tratamento farmacológico , Lactação/efeitos dos fármacos , Mães , Adulto , Aleitamento Materno/métodos , Moduladores de Receptor Estrogênico/farmacologia , Moduladores de Receptor Estrogênico/uso terapêutico , Estrogênios/farmacologia , Estrogênios/uso terapêutico , Feminino , Galactagogos/farmacologia , Galactagogos/uso terapêutico , Humanos , Lactação/fisiologia , Masculino , Resultado do Tratamento
4.
Cell Metab ; 23(4): 591-601, 2016 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-26916363

RESUMO

Although 5%-10% weight loss is routinely recommended for people with obesity, the precise effects of 5% and further weight loss on metabolic health are unclear. We conducted a randomized controlled trial that evaluated the effects of 5.1% ± 0.9% (n = 19), 10.8% ± 1.3% (n = 9), and 16.4% ± 2.1% (n = 9) weight loss and weight maintenance (n = 14) on metabolic outcomes. 5% weight loss improved adipose tissue, liver and muscle insulin sensitivity, and ß cell function, without a concomitant change in systemic or subcutaneous adipose tissue markers of inflammation. Additional weight loss further improved ß cell function and insulin sensitivity in muscle and caused stepwise changes in adipose tissue mass, intrahepatic triglyceride content, and adipose tissue expression of genes involved in cholesterol flux, lipid synthesis, extracellular matrix remodeling, and oxidative stress. These results demonstrate that moderate 5% weight loss improves metabolic function in multiple organs simultaneously, and progressive weight loss causes dose-dependent alterations in key adipose tissue biological pathways.


Assuntos
Tecido Adiposo/fisiopatologia , Resistência à Insulina , Obesidade/fisiopatologia , Redução de Peso , Tecido Adiposo/metabolismo , Adulto , Feminino , Humanos , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Fígado/metabolismo , Fígado/fisiopatologia , Masculino , Pessoa de Meia-Idade , Músculos/metabolismo , Músculos/fisiopatologia , Obesidade/metabolismo
5.
J Clin Invest ; 125(2): 787-95, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25555214

RESUMO

BACKGROUND. Obesity is associated with insulin resistance and increased intrahepatic triglyceride (IHTG) content, both of which are key risk factors for diabetes and cardiovascular disease. However, a subset of obese people does not develop these metabolic complications. Here, we tested the hypothesis that people defined by IHTG content and insulin sensitivity as "metabolically normal obese" (MNO), but not those defined as "metabolically abnormal obese" (MAO), are protected from the adverse metabolic effects of weight gain. METHODS. Body composition, multiorgan insulin sensitivity, VLDL apolipoprotein B100 (apoB100) kinetics, and global transcriptional profile in adipose tissue were evaluated before and after moderate (~6%) weight gain in MNO (n = 12) and MAO (n = 8) subjects with a mean BMI of 36 ± 4 kg/m2 who were matched for BMI and fat mass. RESULTS. Although the increase in body weight and fat mass was the same in both groups, hepatic, skeletal muscle, and adipose tissue insulin sensitivity deteriorated, and VLDL apoB100 concentrations and secretion rates increased in MAO, but not MNO, subjects. Moreover, biological pathways and genes associated with adipose tissue lipogenesis increased in MNO, but not MAO, subjects. CONCLUSIONS. These data demonstrate that MNO people are resistant, whereas MAO people are predisposed, to the adverse metabolic effects of moderate weight gain and that increased adipose tissue capacity for lipogenesis might help protect MNO people from weight gain-induced metabolic dysfunction. TRIAL REGISTRATION. ClinicalTrials.gov NCT01184170. FUNDING. This work was supported by NIH grants UL1 RR024992 (Clinical Translational Science Award), DK 56341 (Nutrition and Obesity Research Center), DK 37948 and DK 20579 (Diabetes Center Grant), and UL1 TR000450 (KL2 Award); a Central Society for Clinical and Translational Research Early Career Development Award; and by grants from the Longer Life Foundation and the Kilo Foundation.


Assuntos
Tecido Adiposo , Adiposidade , Índice de Massa Corporal , Resistência à Insulina , Lipogênese , Obesidade , Tecido Adiposo/metabolismo , Tecido Adiposo/fisiopatologia , Adulto , Apolipoproteína B-100/sangue , Feminino , Humanos , Lipoproteínas VLDL/sangue , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Obesidade/sangue , Obesidade/fisiopatologia
6.
Diabetes Technol Ther ; 15(6): 455-60, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23617251

RESUMO

AIMS: It is necessary to evaluate glucose variability and postprandial hyperglycemia in patients with well-controlled type 2 diabetes mellitus because of the limitations associated with hemoglobin A1c (HbA1c) measurements. We evaluated parameters reflecting postprandial hyperglycemia and glycemic variability in patients with optimal HbA1c. PATIENTS AND METHODS: Thirty-nine patients with HbA1c levels below 7% were recruited to the study. A continuous glucose monitoring system (CGMS) was applied for two 72-h periods. 1,5-Anhydroglucitol (1,5-AG) and fructosamine (FA) were measured as parameters for postprandial hyperglycemia and glucose variability. Using CGMS data, the following postprandial hyperglycemia parameters were calculated: mean postprandial maximum glucose (MPMG) and area under the curve for glucose above 180 mg/dL (AUC-180). To measure glycemic variability, we calculated mean amplitude of glucose excursion (MAGE) using a classical (MAGEc) and new method (MAGE group of sign [MAGEgos]). RESULTS: The baseline HbA1c level was 6.3±0.3%. The mean MPMG was 10.34±1.84 mmol/L, and the mean AUC-180 was 0.17±0.23 mmol/L/day. The mean MAGEgos was 3.27±1.29 mmol/L, and MAGEc was 4.30±1.43 mmol/L, indicating glycemic variability in our patients. The mean levels of 1,5-AG and FA were 16.7±7.4 µg/mL and 273.0±22.5 µmol/L, respectively. In a correlation analysis, FA was significantly correlated with MPMG, AUC-180, MAGEgos, and MAGEc. In contrast, 1,5-AG was only correlated with AUC-180. CONCLUSIONS: This study demonstrated postprandial hyperglycemia and glycemic variability in subjects with well-controlled diabetes. FA may reflect postprandial hyperglycemia and glycemic variability, but 1,5-AG may be of limited value for assessing glucose variability in patients with well-controlled type 2 diabetes mellitus.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Hiperglicemia/sangue , Programas de Rastreamento/métodos , Adolescente , Adulto , Idoso , Análise de Variância , Área Sob a Curva , Biomarcadores/sangue , Automonitorização da Glicemia , Desoxiglucose/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Frutosamina/sangue , Hemoglobinas Glicadas/metabolismo , Humanos , Hiperglicemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , República da Coreia/epidemiologia
7.
Cardiorenal Med ; 2(3): 211-217, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22969777

RESUMO

BACKGROUND: Niaspan® (extended-release niacin) is a nicotinic acid formulation used to treat dyslipidemia in obese subjects. Niaspan binds to the GPR109A receptor in adipose tissue and stimulates adiponectin secretion, which should improve insulin sensitivity. However, Niaspan therapy often causes insulin resistance. The purpose of this study was to evaluate whether Niaspan-induced changes in plasma adiponectin concentration are associated with a blunting of Niaspan's adverse effect on insulin action in obese subjects with non-alcoholic fatty liver disease (NAFLD). METHODS: A hyperinsulinemic-euglycemic clamp procedure was used to assess muscle insulin sensitivity before and after 16 weeks of Niaspan therapy in 9 obese subjects with NAFLD [age 43 ± 5 years; BMI 35.1 ± 1.3 (means ± SEM)]. RESULTS: Niaspan therapy did not affect body weight (99.1 ± 4.2 vs. 100 ± 4.4 kg) or percent body fat (37.8 ± 2.5 vs. 37.0 ± 2.5%). However, Niaspan therapy caused a 22% reduction in insulin-mediated glucose disposal (p < 0.05). The deterioration in glucose disposal was inversely correlated with the Niaspan-induced increase in plasma adiponectin concentration (r = 0.67, p = 0.05). CONCLUSIONS: These results demonstrate that Niaspan causes skeletal muscle insulin resistance, independent of changes in body weight or body fat, and the Niaspan-induced increase in plasma adiponectin concentration might partially ameliorate Niaspan's adverse effect on insulin action in obese subjects with NAFLD.

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