scholarly journals Disassociation of Liver and Muscle Insulin Resistance from Ectopic Lipid Accumulation in Low-Birth-Weight Individuals

2011 ◽  
Vol 96 (12) ◽  
pp. 3873-3880 ◽  
Author(s):  
Sylvie Dufour ◽  
Kitt Falk Petersen
Keyword(s):  
Insulin Resistance ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Lipid Accumulation ◽  
Muscle Insulin Resistance

scholarly journals Macrophage colony-stimulating factor increases hepatic macrophage content, liver growth, and lipid accumulation in neonatal rats

2018 ◽  
Vol 314 (3) ◽  
pp. G388-G398 ◽  
Author(s):  
Clare Pridans ◽  
Kristin A. Sauter ◽  
Katharine M. Irvine ◽  
Gemma M. Davis ◽  
Lucas Lefevre ◽  
...  
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Kupffer Cell ◽  
Lipid Accumulation ◽  
Cell Expansion ◽  
Somatic Growth ◽  
Hepatocyte Proliferation ◽  
Neonatal Rats ◽  
Colony Stimulating Factor ◽  
Stimulating Factor

Signaling via the colony-stimulating factor 1 receptor (CSF1R) controls the survival, differentiation, and proliferation of macrophages. Mutations in CSF1 or CSF1R in mice and rats have pleiotropic effects on postnatal somatic growth. We tested the possible application of pig CSF1-Fc fusion protein as a therapy for low birth weight (LBW) at term, using a model based on maternal dexamethasone treatment in rats. Neonatal CSF1-Fc treatment did not alter somatic growth and did not increase the blood monocyte count. Instead, there was a substantial increase in the size of liver in both control and LBW rats, and the treatment greatly exacerbated lipid droplet accumulation seen in the dexamethasone LBW model. These effects were reversed upon cessation of treatment. Transcriptional profiling of the livers supported histochemical evidence of a large increase in macrophages with a resident Kupffer cell phenotype and revealed increased expression of many genes implicated in lipid droplet formation. There was no further increase in hepatocyte proliferation over the already high rates in neonatal liver. In conclusion, treatment of neonatal rats with CSF1-Fc caused an increase in liver size and hepatic lipid accumulation, due to Kupffer cell expansion and/or activation rather than hepatocyte proliferation. Increased liver macrophage numbers and expression of endocytic receptors could mitigate defective clearance functions in neonates.NEW & NOTEWORTHY This study is based on extensive studies in mice and pigs of the role of CSF1/CSF1R in macrophage development and postnatal growth. We extended the study to neonatal rats as a possible therapy for low birth weight. Unlike our previous studies in mice and pigs, there was no increase in hepatocyte proliferation and no increase in monocyte numbers. Instead, neonatal rats treated with CSF1 displayed reversible hepatic steatosis and Kupffer cell expansion.

scholarly journals Escitalopram Ameliorates Hypercortisolemia and Insulin Resistance in Low Birth Weight Men With Limbic Brain Alterations

2017 ◽  
Vol 103 (1) ◽  
pp. 115-124 ◽  
Author(s):  
Christian Selmer Buhl ◽  
Hans Stødkilde-Jørgensen ◽  
Poul Videbech ◽  
Allan Vaag ◽  
Niels Møller ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Birth Weight ◽  
Low Birth Weight

scholarly journals Treatment with an SSRI antidepressant restores hippocampo-hypothalamic corticosteroid feedback and reverses insulin resistance in low-birth-weight rats

2010 ◽  
Vol 298 (5) ◽  
pp. E920-E929 ◽  
Author(s):  
Esben S. Buhl ◽  
Thomas Korgaard Jensen ◽  
Niels Jessen ◽  
Betina Elfving ◽  
Christian S. Buhl ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Birth Weight ◽  
Insulin Sensitivity ◽  
Low Birth Weight ◽  
Mrna Expression ◽  
Hpa Axis ◽  
Whole Body ◽  
Oral Glucose ◽  
Red Muscle ◽  
Hpa Axis Activity

Low birth weight (LBW) is associated with type 2 diabetes and depression, which may be related to prenatal stress and insulin resistance as a result of chronic hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. We examined whether treatment with a selective serotonin reuptake inhibitor [escitalopram (ESC)] could downregulate HPA axis activity and restore insulin sensitivity in LBW rats. After 4–5 wk of treatment, ESC-exposed LBW (SSRI-LBW) and saline-treated control and LBW rats (Cx and LBW) underwent an oral glucose tolerance test or a hyperinsulinemic euglycemic clamp to assess whole body insulin sensitivity. Hepatic phospho enolpyruvate carboxykinase (PEPCK) mRNA expression and red skeletal muscle PKB Ser473phosphorylation were used to assess tissue-specific insulin sensitivity. mRNA expression of the hypothalamic mineralocorticoid receptor was fivefold upregulated in LBW ( P < 0.05 vs. Cx), accompanied by increased corticosterone release during restraint stress and total 24-h urinary excretion ( P < 0.05 vs. Cx), whole body insulin resistance ( P < 0.001 vs. Cx), and impaired insulin suppression of hepatic PEPCK mRNA expression ( P < 0.05 vs. Cx). Additionally, there was a tendency for reduced red muscle PKB Ser473phosphorylation. The ESC treatment normalized corticosterone secretion ( P < 0.05 vs. LBW), whole body insulin sensitivity ( P < 0.01) as well as postprandial suppression of hepatic mRNA PEPCK expression ( P < 0.05), and red muscle PKB Ser473phosphorylation ( P < 0.01 vs. LBW). We conclude that these data suggest that the insulin resistance and chronic HPA axis hyperactivity in LBW rats can be reversed by treatment with an ESC, which downregulates HPA axis activity, lowers glucocorticoid exposure, and restores insulin sensitivity in LBW rats.

Obesity, hormonal and metabolic abnormalities in adolescent girls with polycystic ovary syndrome

2013 ◽  
Vol 154 (31) ◽  
pp. 1226-1234
Author(s):  
László Ságodi ◽  
Béla Lombay ◽  
Ildikó Vámosi ◽  
László Barkai
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Body Mass Index ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Polycystic Ovary Syndrome ◽  
Adolescent Girls ◽  
Polycystic Ovary ◽  
Metabolic Abnormalities ◽  
Ovary Syndrome

Introduction: Polycystic ovary syndrome is associated with metabolic abnormalities, such as dyslipidemia, obesity, glucose intolerance, which are also components of the metabolic syndrome. Central obesity and insulin resistance appear to play an important role in the pathogenesis of polycystic ovary syndrome, perhaps via subsequent steroidogenic dysregulation. Aim: The aim of the authors was to assess metabolic and hormonal abnormalities in adolescent girls with polycystic ovary syndrome. Method: The study included 52 adolescents diagnosed with polycystic ovary syndrome based on the Rotterdam criteria. Anthropometric, hormonal and metabolic parameters were evaluated among all subjects. 20 healthy, age-matched, non-obese, regularly menstruating girls were used as controls. Of the 52 patients, 15 patients were born with low-birth-weight and 37 patients were born with normal birth weight. Oral glucose tolerance test was performed in all patients and controls. The age of patients was 16.8±3.1 years, and the age of controls was 16.95±2.1 years. Results: Among patients with polycystic ovary syndrome the prevalence of overweight and obesity was 35% (n = 18), while impaired fasting glucose occurred in one patient, impaired glucose tolerance in 8 patients, insulin resistance in 25 patients and metabolic syndrome in 12 patients. Serum triglyceride levels in patients and controls were 1.4±0.8 and 0.9±0.3 mmol/l, respectively (p<0.05), while fasting blood glucose, total cholesterol, HDL and LDL cholesterol were not different in the two groups. Metabolic abnormalities and obesity were more severe and more frequent in patients with low-birth-weight compared to those born with normal weight. There was a negative correlation between birth weight and body mass index SDS values and a positive correlation between fasting insulin levels and body mass index SDS (r = 0.37) in patients born with low-birth-weight. Conclusions: Abnormal glucose metabolism is frequently present in adolescents with polycystic ovary syndrome. It is possible that early diagnosis of polycystic ovary syndrome in adolescences may prevent some of the long-term complications associated with this syndrome. Orv. Hetil., 2013, 154, 1226–1234.

scholarly journals Increased hypothalamic-pituitary-adrenal axis activity and hepatic insulin resistance in low-birth-weight rats

2007 ◽  
Vol 293 (5) ◽  
pp. E1451-E1458 ◽  
Author(s):  
Esben S. Buhl ◽  
Susanne Neschen ◽  
Shin Yonemitsu ◽  
Joerg Rossbacher ◽  
Dongyan Zhang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Birth Weight ◽  
Insulin Sensitivity ◽  
Low Birth Weight ◽  
Hepatic Insulin Resistance ◽  
Hypothalamic Pituitary Adrenal ◽  
Adrenal Axis ◽  
Pituitary Adrenal Axis

Individuals born with a low birth weight (LBW) have an increased prevalence of type 2 diabetes, but the mechanisms responsible for this association are unknown. Given the important role of insulin resistance in the pathogenesis of type 2 diabetes, we examined insulin sensitivity in a rat model of LBW due to intrauterine fetal stress. During the last 7 days of gestation, rat dams were treated with dexamethasone and insulin sensitivity was assessed in the LBW offspring by a hyperinsulinemic euglycemic clamp. The LBW group had liver-specific insulin resistance associated with increased levels of PEPCK expression. These changes were associated with pituitary hyperplasia of the ACTH-secreting cells, increased morning plasma ACTH concentrations, elevated corticosterone secretion during restraint stress, and an ∼70% increase in 24-h urine corticosterone excretion. These data support the hypothesis that prenatal stress can result in chronic hyperactivity of the hypothalamic-pituitary-adrenal axis, resulting in increased plasma corticosterone concentrations, upregulation of hepatic gluconeogenesis, and hepatic insulin resistance.

scholarly journals Mitochondrial-Targeted Catalase Protects Against High-Fat Diet–Induced Muscle Insulin Resistance by Decreasing Intramuscular Lipid Accumulation

Diabetes ◽  
2017 ◽  
Vol 66 (8) ◽  
pp. 2072-2081 ◽  
Author(s):  
Hui-Young Lee ◽  
Jae Sung Lee ◽  
Tiago Alves ◽  
Warren Ladiges ◽  
Peter S. Rabinovitch ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
High Fat ◽  
Muscle Insulin Resistance ◽  
Intramuscular Lipid

scholarly journals Decreased insulin sensitivity in small for gestational age males treated with GH and preterm untreated males: a study in young adults.

2008 ◽  
Vol 158 (6) ◽  
pp. 899-904 ◽  
Author(s):  
J Rotteveel ◽  
M M van Weissenbruch ◽  
H A Delemarre-Van de Waal
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Birth Weight ◽  
Insulin Sensitivity ◽  
Low Birth Weight ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Gh Therapy ◽  
The Metabolic Syndrome ◽  
Preterm Born

BackgroundLow birth weight and preterm birth are associated with growth delay as well as the development of insulin resistance. Insulin resistance is especially seen in subjects with catch-up growth. GH therapy induces growth in short subjects with low birth weight at term, but little is known about the long-term effects on insulin sensitivity. GH therapy is now also proposed for preterms that remain short.MethodsWe investigated insulin sensitivity using the gold standard hyperinsulinemic-euglycemic clamp technique in 10 young adult males born small for gestational age (SGA) who had been treated with GH during childhood (GH) in comparison with 15 males born preterm AGA (premAGA), 13 males born preterm SGA (premSGA), and 15 males born at term with normal birth weight (CON). Furthermore, we investigated the presence of the metabolic syndrome.ResultsInsulin sensitivity was decreased in premAGA, premSGA, and GH subjects compared with CON males. The metabolic syndrome was not present in any of the groups.ConclusionInsulin sensitivity is decreased in GH-treated SGA born males as well as in preterm born males. With respect to the SGA subjects, whether the difference results from perinatal-, postnatal-, or GH therapy-related factors are not known. With respect to the preterm born subjects, close surveillance is needed when commencing GH therapy.

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