Overfeeding Dairy Cattle during Late-Pregnancy Alters Hepatic PPARα-Regulated Pathways Including Hepatokines: Impact on Metabolism and Peripheral Insulin Sensitivity

Here, we tested the hypothesis that excess maternal androgen in late pregnancy reduces placental and fetal growth, increases placental steroidogenesis, and adversely affects glucose and lipid metabolism in adult female offspring. Pregnant Wistar rats were randomly assigned to treatment with testosterone (daily injections of 5 mg of free testosterone from gestational days 16 to 19) or vehicle alone. In experiment 1, fetal and placental weights, circulating maternal testosterone, estradiol, and corticosterone levels, and placental protein expression and distribution of estrogen receptor-α and -β, androgen receptor, and 17β-hydroxysteroid dehydrogenase 2 were determined. In experiment 2, birth weights, postnatal growth rates, circulating testosterone, estradiol, and corticosterone levels, insulin sensitivity, adipocyte size, lipid profiles, and the presence of nonalcoholic fatty liver were assessed in female adult offspring. Treatment with testosterone reduced placental and fetal weights and increased placental expression of all four proteins. The offspring of testosterone-treated dams were born with intrauterine growth restriction; however, at 6 wk of age there was no difference in body weight between the offspring of testosterone- and control-treated rats. At 10–11 wk of age, the offspring of the testosterone-treated dams had less fat mass and smaller adipocyte size than those born to control rats and had no difference in insulin sensitivity. Circulating triglyceride levels were higher in the offspring of testosterone-treated dams, and they developed nonalcoholic fatty liver as adults. We demonstrate for the first time that prenatal testosterone exposure alters placental steroidogenesis and leads to dysregulation of lipid metabolism in their adult female offspring.

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Dietary Lipid during Late-Pregnancy and Early-Lactation to Manipulate Metabolic and Inflammatory Gene Network Expression in Dairy Cattle Liver with a Focus on PPARs

Gene Regulation and Systems Biology ◽

10.4137/grsb.s12005 ◽

2013 ◽

Vol 7 ◽

pp. GRSB.S12005 ◽

Cited By ~ 4

Author(s):

Haji Akbar ◽

Eduardo Schmitt ◽

Michael A. Ballou ◽

Marcio N. Corrêa ◽

Edward J. DePeters ◽

...

Keyword(s):

Dairy Cattle ◽

Gene Network ◽

Late Pregnancy ◽

Dietary Lipid ◽

Early Lactation ◽

Inflammatory Gene

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RHIGF-I administration increases in vivo peripheral insulin sensitivity in adults with type 1 diabetes mellitus

Growth Hormone & IGF Research ◽

10.1016/s1096-6374(98)80144-5 ◽

1998 ◽

Vol 8 (4) ◽

pp. 315

Author(s):

PV Carroll ◽

ER Christ ◽

I Gowrie ◽

R Hovorka ◽

DL Russell-Jones ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Insulin Sensitivity ◽

Type 1 Diabetes Mellitus ◽

Peripheral Insulin Sensitivity

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Plasma cathepsin D activity is negatively associated with hepatic insulin sensitivity in overweight and obese humans

Diabetologia ◽

10.1007/s00125-019-05025-2 ◽

2019 ◽

Vol 63 (2) ◽

pp. 374-384 ◽

Cited By ~ 3

Author(s):

Lingling Ding ◽

Gijs H. Goossens ◽

Yvonne Oligschlaeger ◽

Tom Houben ◽

Ellen E. Blaak ◽

...

Keyword(s):

Insulin Sensitivity ◽

Cathepsin D ◽

Insulin Infusion ◽

Hepatic Insulin Sensitivity ◽

Euglycaemic Clamp ◽

Negatively Associated ◽

Peripheral Insulin Sensitivity ◽

Hyperinsulinaemic Euglycaemic Clamp ◽

Tnf Α ◽

Glucose Output

Abstract Aims/hypothesis Insulin resistance in skeletal muscle and liver plays a major role in the pathophysiology of type 2 diabetes. The hyperinsulinaemic–euglycaemic clamp is considered the gold standard for assessing peripheral and hepatic insulin sensitivity, yet it is a costly and labour-intensive procedure. Therefore, easy-to-measure, cost-effective approaches to determine insulin sensitivity are needed to enable organ-specific interventions. Recently, evidence emerged that plasma cathepsin D (CTSD) is associated with insulin sensitivity and hepatic inflammation. Here, we aimed to investigate whether plasma CTSD is associated with hepatic and/or peripheral insulin sensitivity in humans. Methods As part of two large clinical trials (one designed to investigate the effects of antibiotics, and the other to investigate polyphenol supplementation, on insulin sensitivity), 94 overweight and obese adults (BMI 25–35 kg/m2) previously underwent a two-step hyperinsulinaemic–euglycaemic clamp (using [6,6-2H2]glucose) to assess hepatic and peripheral insulin sensitivity (per cent suppression of endogenous glucose output during the low-insulin-infusion step, and the rate of glucose disappearance during high-insulin infusion [40 mU/(m2 × min)], respectively). In this secondary analysis, plasma CTSD levels, CTSD activity and plasma inflammatory cytokines were measured. Results Plasma CTSD levels were positively associated with the proinflammatory cytokines IL-8 and TNF-α (IL-8: standardised β = 0.495, p < 0.001; TNF-α: standardised β = 0.264, p = 0.012). Plasma CTSD activity was negatively associated with hepatic insulin sensitivity (standardised β = −0.206, p = 0.043), independent of age, sex, BMI and waist circumference, but it was not associated with peripheral insulin sensitivity. However, plasma IL-8 and TNF-α were not significantly correlated with hepatic insulin sensitivity. Conclusions/interpretation We demonstrate that plasma CTSD activity, but not systemic inflammation, is inversely related to hepatic insulin sensitivity, suggesting that plasma CTSD activity may be used as a non-invasive marker for hepatic insulin sensitivity in humans.

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Metformin Improves Peripheral Insulin Sensitivity in Youth With Type 1 Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2019-00129 ◽

2019 ◽

Vol 104 (8) ◽

pp. 3265-3278 ◽

Cited By ~ 15

Author(s):

Melanie Cree-Green ◽

Bryan C Bergman ◽

Eda Cengiz ◽

Larry A Fox ◽

Tamara S Hannon ◽

...

Keyword(s):

Type 1 Diabetes ◽

Insulin Sensitivity ◽

Peripheral Insulin Sensitivity

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Obesity Status Affects the Relationship Between Protein Intake and Insulin Sensitivity in Late Pregnancy

Nutrients ◽

10.3390/nu11092190 ◽

2019 ◽

Vol 11 (9) ◽

pp. 2190 ◽

Cited By ~ 2

Author(s):

Allman ◽

Diaz Fuentes ◽

Williams ◽

Turner ◽

Andres ◽

...

Keyword(s):

Insulin Sensitivity ◽

Early Pregnancy ◽

Dietary Protein ◽

Protein Intake ◽

Late Pregnancy ◽

Oral Glucose ◽

Metabolic Clearance ◽

Dietary Protein Intake ◽

Food Record ◽

The Relationship

The purpose of this study was to determine the associations between amount and type of dietary protein intake and insulin sensitivity in late pregnancy, in normal weight and overweight women (29.8 ± 0.2 weeks gestation, n = 173). A 100-gram oral glucose tolerance test (OGTT) was administered following an overnight fast to estimate the metabolic clearance rate of glucose (MCR, mg · kg-1 · min-1) using four different equations accounting for the availability of blood samples. Total (TP), animal (AP), and plant (PP) protein intakes were assessed using a 3-day food record. Two linear models with MCR as the response variable were fitted to the data to estimate the relationship of protein intake to insulin sensitivity either unadjusted or adjusted for early pregnancy body mass index (BMI) because of the potential of BMI to influence this relationship. There was a positive association between TP (β = 1.37, p = 0.002) and PP (β = 4.44, p < 0.001) intake in the last trimester of pregnancy and insulin sensitivity that weakened when accounting for early pregnancy BMI. However, there was no relationship between AP intake and insulin sensitivity (β = 0.95, p = 0.08). Therefore, early pregnancy BMI may be a better predictor of insulin sensitivity than dietary protein intake in late pregnancy.

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