scholarly journals Maternal Metformin Intervention during Obese Glucose-Intolerant Pregnancy Affects Adiposity in Young Adult Mouse Offspring in a Sex-Specific Manner

2021 ◽  
Vol 22 (15) ◽  
pp. 8104
Author(s):  
Josca M. Schoonejans ◽  
Heather L. Blackmore ◽  
Thomas J. Ashmore ◽  
Catherine E. Aiken ◽  
Denise S. Fernandez-Twinn ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Maternal Obesity ◽  
Macrophage Infiltration ◽  
Gestation Length ◽  
Specific Effects ◽  
Obesogenic Diet ◽  
Adipocyte Hypertrophy ◽  
Excessive Adiposity ◽  
Similar Body ◽  
Adipocyte Hyperplasia

Background: Metformin is commonly used to treat gestational diabetes mellitus. This study investigated the effect of maternal metformin intervention during obese glucose-intolerant pregnancy on the gonadal white adipose tissue (WAT) of 8-week-old male and female mouse offspring. Methods: C57BL/6J female mice were provided with a control (Con) or obesogenic diet (Ob) to induce pre-conception obesity. Half the obese dams were treated orally with 300 mg/kg/d of metformin (Ob-Met) during pregnancy. Gonadal WAT depots from 8-week-old offspring were investigated for adipocyte size, macrophage infiltration and mRNA expression of pro-inflammatory genes using RT-PCR. Results: Gestational metformin attenuated the adiposity in obese dams and increased the gestation length without correcting the offspring in utero growth restriction and catch-up growth caused by maternal obesity. Despite similar body weight, the Ob and Ob-Met offspring of both sexes showed adipocyte hypertrophy in young adulthood. Male Ob-Met offspring had increased WAT depot weight (p < 0.05), exaggerated adipocyte hyperplasia (p < 0.05 vs. Con and Ob offspring), increased macrophage infiltration measured via histology (p < 0.05) and the mRNA expression of F4/80 (p < 0.05). These changes were not observed in female Ob-Met offspring. Conclusions: Maternal metformin intervention during obese pregnancy causes excessive adiposity, adipocyte hyperplasia and WAT inflammation in male offspring, highlighting sex-specific effects of prenatal metformin exposure on offspring WAT.

scholarly journals Maternal Obesity During Pregnancy and Lactation Influences Offspring Obesogenic Adipogenesis but Not Developmental Adipogenesis in Mice

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 495 ◽  
Author(s):  
Dyan Sellayah ◽  
Hugh Thomas ◽  
Stuart Lanham ◽  
Felino Cagampang
Keyword(s):  
Maternal Obesity ◽  
Adipogenic Differentiation ◽  
High Fat ◽  
Health Crisis ◽  
Culture Models ◽  
Pregnancy And Lactation ◽  
Adipocyte Hypertrophy ◽  
Adipocyte Hyperplasia ◽  
Cell Culture Models

Obesity is an escalating health crisis of pandemic proportions and by all accounts it has yet to reach its peak. Growing evidence suggests that obesity may have its origins in utero. Recent studies have shown that maternal obesity during pregnancy may promote adipogenesis in offspring. However, these studies were largely based on cell culture models. Whether or not maternal obesity impacts on offspring adipogenesis in vivo remains to be fully established. Furthermore, in vivo adipogenic differentiation has been shown to happen at distinct time periods, one during development (developmental adipogenesis—which is complete by 4 weeks of age in mice) and another in adulthood in response to feeding a high-fat (HF) diet (obesogenic adipogenesis). We therefore set out to determine whether maternal obesity impacted on offspring adipocyte hyperplasia in vivo and whether maternal obesity impacted on developmental or obesogenic adipogenesis, or both. Our findings reveal that maternal obesity is associated with enhanced obesogenic adipogenesis in HF-fed offspring. Interestingly, in newly weaned (4-week-old) offspring, maternal obesity is associated with adipocyte hypertrophy, but there were no changes in adipocyte number. Our results suggest that maternal obesity impacts on offspring obesogenic adipogenesis but does not affect developmental adipogenesis.

scholarly journals Mechanisms Underlying the Cognitive and Behavioural Effects of Maternal Obesity

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 240
Author(s):  
Kyoko Hasebe ◽  
Michael D. Kendig ◽  
Margaret J. Morris
Keyword(s):  
Animal Models ◽  
Adverse Effects ◽  
Gut Microbiome ◽  
Maternal Obesity ◽  
Maternal Diet ◽  
Affective State ◽  
Brain Regions ◽  
Brain Network ◽  
Physical And Mental Health ◽  
Obesogenic Diet

The widespread consumption of ‘western’-style diets along with sedentary lifestyles has led to a global epidemic of obesity. Epidemiological, clinical and preclinical evidence suggests that maternal obesity, overnutrition and unhealthy dietary patterns programs have lasting adverse effects on the physical and mental health of offspring. We review currently available preclinical and clinical evidence and summarise possible underlying neurobiological mechanisms by which maternal overnutrition may perturb offspring cognitive function, affective state and psychosocial behaviour, with a focus on (1) neuroinflammation; (2) disrupted neuronal circuities and connectivity; and (3) dysregulated brain hormones. We briefly summarise research implicating the gut microbiota in maternal obesity-induced changes to offspring behaviour. In animal models, maternal obesogenic diet consumption disrupts CNS homeostasis in offspring, which is critical for healthy neurodevelopment, by altering hypothalamic and hippocampal development and recruitment of glial cells, which subsequently dysregulates dopaminergic and serotonergic systems. The adverse effects of maternal obesogenic diets are also conferred through changes to hormones including leptin, insulin and oxytocin which interact with these brain regions and neuronal circuits. Furthermore, accumulating evidence suggests that the gut microbiome may directly and indirectly contribute to these maternal diet effects in both human and animal studies. As the specific pathways shaping abnormal behaviour in offspring in the context of maternal obesogenic diet exposure remain unknown, further investigations are needed to address this knowledge gap. Use of animal models permits investigation of changes in neuroinflammation, neurotransmitter activity and hormones across global brain network and sex differences, which could be directly and indirectly modulated by the gut microbiome.

scholarly journals Sexual Dimorphism in Changes That Occur in Tissues, Organs and Plasma during the Early Stages of Obesity Development

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 717
Author(s):  
Priyanka Dhanraj ◽  
Marlene B. van Heerden ◽  
Michael S. Pepper ◽  
Melvin A. Ambele
Keyword(s):  
Weight Gain ◽  
Sexual Dimorphism ◽  
Macrophage Infiltration ◽  
Health Concern ◽  
Gm Csf ◽  
Early Stages ◽  
Cytokine Levels ◽  
Adipocyte Hypertrophy ◽  
Plasma Hormones ◽  
Clinical Changes

Despite obesity being a major health concern, information on the early clinical changes that occur in plasma and tissues during obesity development and the influence of sexual dimorphism is lacking. This study investigated changes in tissue and organ histology, macrophage infiltration, plasma hormones, lipid, and chemokine and cytokine levels in mice fed on a high fat diet for 11-weeks. An increase in adiposity, accompanied by adipocyte hypertrophy and macrophage infiltration, was observed to be significantly greater in males than females. Important changes in cell morphology and histology were noted in the lungs, liver, kidney, spleen, and heart, which may indicate early signs for developing obesity associated comorbidities. Leptin, but not adiponectin, was significantly altered during weight gain. Additionally, leptin, but not adiposity, correlated with insulin levels. Interestingly, GM-CSF, TNFα, and IL-12 (p70) were not produced in the early stages of obesity development. Meanwhile, the production of MCP-1, IP-10, RANTES, IL-10, IL-6, KC, and IL-9 were greatly influenced by sexual dimorphism. Importantly, IL-6/IL-10 axis of anti-inflammatory cytokine regulation was observed only in females and may account for their significantly lower weight gain compared to males. This study provides new knowledge on how sexual dimorphism may influence the development of obesity and associated comorbidities.

Placental insufficiency induces a sexually dimorphic response in the expression of cardiac growth and metabolic signalling molecules upon exposure to a postnatal western diet in guinea pigs

2021 ◽  
pp. 1-13
Author(s):  
Jack R.T. Darby ◽  
Jacky Chiu ◽  
Timothy R.H. Regnault ◽  
Janna L. Morrison
Keyword(s):  
Birth Weight ◽  
Mrna Expression ◽  
Female Offspring ◽  
Postnatal Life ◽  
Sexually Dimorphic ◽  
Fibrotic Response ◽  
Cardiac Growth ◽  
Signalling Molecules ◽  
Secondary Insult ◽  
Obesogenic Diet

Abstract There is a strong relationship between low birth weight (LBW) and an increased risk of developing cardiovascular disease (CVD). In postnatal life, LBW offspring are becoming more commonly exposed to the additional independent CVD risk factors, such as an obesogenic diet. However, how an already detrimentally programmed LBW myocardium responds to a secondary insult, such as an obesogenic diet (western diet; WD), during postnatal life is ill defined. Herein, we aimed to determine in a pre-clinical guinea pig model of CVD, both the independent and interactive effects of LBW and a postnatal WD on the molecular pathways that regulate cardiac growth and metabolism. Uterine artery ablation was used to induce placental insufficiency (PI) in pregnant guinea pigs to generate LBW offspring. Normal birth weight (NBW) and LBW offspring were weaned onto either a Control diet or WD. At ˜145 days after birth (young adulthood), male and female offspring were humanely killed, the heart weighed and left ventricle tissue collected. The mRNA expression of signalling molecules involved in a pathological hypertrophic and fibrotic response was increased in the myocardium of LBW male, but not female offspring, fed a WD as was the mRNA expression of transcription factors involved in fatty acid oxidation. The mRNA expression of glucose transporters was downregulated by LBW and WD in male, but not female hearts. This study has highlighted a sexually dimorphic cardiac pathological hypertrophic and fibrotic response to the secondary insult of postnatal WD consumption in LBW offspring.

scholarly journals Adipose tissue: from amorphous filler to metabolic mastermind

2021 ◽  
Author(s):  
Silvia Corvera
Keyword(s):  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Disease Risk ◽  
Appetite Control ◽  
Fat Storage ◽  
Fuel Distribution ◽  
Adipose Tissue Depots ◽  
Increased Risk ◽  
Adipocyte Hypertrophy ◽  
Adipocyte Hyperplasia

Adipose tissue plays a central role in the control of systemic glucose homeostasis through two major mechanisms: fat storage and secretion of specific cytokines known as adipokines. Fat storage in adipose tissue is critically important, as it prevents lipid deposition in liver and muscle, which in turn results in insulin resistance and increased risk of type 2 diabetes. Secretion of adipokines, such as leptin, protects from fuel depletion through appetite control, and other adipokines control fuel distribution and utilization. Fat storage capacity of adipose tissue increases through two mechanisms, adipocyte hypertrophy and adipocyte hyperplasia. Adipose tissue depots expand differently in diverse individuals and confer varying degrees of metabolic disease risk. There are multiple adipocyte subtypes that together mediate the functions of adipose tissue. They do so through specialized functions such as thermogenesis, which burns fuel to maintain core temperature, and through selective secretion of different adipokines. Much progress has been made in understanding the mechanisms by which adipose tissue controls systemic metabolism, increasing our hope of developing new, effective therapies for metabolic diseases.

scholarly journals Exercise Intergenerationally Drives Muscle-Based Thermogenesis and Myogenesis in Offspring Impaired Due to Maternal Obesity

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1083-1083
Author(s):  
Jun Seok Son ◽  
Song Ah Chae ◽  
Mei-Jun Zhu ◽  
Min Du
Keyword(s):  
Gene Expression ◽  
Surface Temperature ◽  
Muscle Development ◽  
Maternal Obesity ◽  
Experimental Unit ◽  
Obesogenic Diet ◽  
Maternal Exercise ◽  
The Impact ◽  
Exercise During Pregnancy ◽  
Fetal Muscle

Abstract Objectives Maternal obesity (MO) predisposes metabolic dysfunction in offspring muscle. Skeletal muscle-dependent non-shivering thermogenesis (NST) is emerging as a critical mechanism for maintaining energy homeostasis, but the effects of maternal exercise on muscle-based thermogenesis in offspring remains unexplored. In addition, the impact of maternal obesity and exercise on fetal muscle development is unclear, which will also be examined. The objective of the current study is to explore the effects of maternal exercise on muscle-based thermogenesis and myogenesis in fetuses impaired due to MO. Methods Female C57BL/6 J mice were randomized and assigned to either control (CON, 10 kcal% from fat) or obesogenic diet (OB, 60 kcal% from fat) for 8 weeks to induce obesity and then mated. Then, pregnant mice in obesogenic diet were further separated into two groups with/without exercise (daily 60 min exercise) during pregnancy, which resulted in three treatments: control (CON), OB, and OB-EX (n = 6 per group). Fetal skeletal muscles were collected at embryonic day 18.5 (E18.5). In another cohort of animals, maternal mice were allowed to give birth and surface temperature of neonates was measured. Statistical analysis were conducted using one way analysis of variance (ANOVA); a pregnancy/litter was considered as an experimental unit. Results OB reduced surface temperature of neonates (P &lt; 0.01). In E18.5 fetal muscle, OB downregulated muscle-based thermogenic gene expression (P &lt; 0.05), including Sln, Serca2, and Ryr1. In addition, the expression of mitochondriogenic genes (P &lt; 0.05), including Ppargc1a and Tfam, was also reduced in OB fetal female and male muscle. These adverse changes were prevented due to exercise during pregnancy. Furthermore, maternal exercise protected against the downregulation of myogenesis-related gene expression, including MyoD, Myogenin, Myf5, and Pax7, due to MO. Conclusions Exercise during pregnancy enhanced muscle-based thermogenic gene expression and myogenesis which were impaired due to MO, suggesting that maternal exercise intergenerationally improves metabolic health of offspring. Funding Sources Supported by NIH Grant R01HD067449.

206: Sex-specific effects of maternal obesity on embryo size and fetal brain oxidative stress

2016 ◽  
Vol 214 (1) ◽  
pp. S124-S125 ◽  
Author(s):  
Andrea G. Edlow ◽  
Faycal Guedj ◽  
Deanna Y. Sverdlov ◽  
Caterina Neri ◽  
Sanaya T. Daruvala ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Maternal Obesity ◽  
Fetal Brain ◽  
Embryo Size ◽  
Specific Effects ◽  
Brain Oxidative Stress

Region-specific effects of chronic lithium administration on neuropeptide Y and somatostatin mRNA expression in the rat brain

1995 ◽  
Vol 194 (1-2) ◽  
pp. 89-92 ◽  
Author(s):  
Olof Zachrisson ◽  
Aleksander A. Mathé ◽  
Carina Stenfors ◽  
Nils Lindeforsa
Keyword(s):  
Neuropeptide Y ◽  
Mrna Expression ◽  
Rat Brain ◽  
Specific Effects

scholarly journals Deletion of miRNA-22 Induces Cardiac Hypertrophy in Females but Attenuates Obesogenic Diet-Mediated Metabolic Disorders

2020 ◽  
Vol 54 (6) ◽  
pp. 1199-1217
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Cardiac Hypertrophy ◽  
Mrna Expression ◽  
Metabolic Disorders ◽  
Body Weight Gain ◽  
Expression Profiles ◽  
Left Ventricular ◽  
Sequencing Analysis ◽  
Obesogenic Diet

Background/Aims: Obesity is a risk factor associated with cardiometabolic complications. Recently, we reported that miRNA-22 deletion attenuated high-fat diet-induced adiposity and prevented dyslipidemia without affecting cardiac hypertrophy in male mice. In this study, we examined the impact of miRNA-22 in obesogenic diet-induced cardiovascular and metabolic disorders in females. Methods: Wild type (WT) and miRNA-22 knockout (miRNA-22 KO) females were fed a control or an obesogenic diet. Body weight gain, adiposity, glucose tolerance, insulin tolerance, and plasma levels of total cholesterol and triglycerides were measured. Cardiac and white adipose tissue remodeling was assessed by histological analyses. Echocardiography was used to evaluate cardiac function and morphology. RNA-sequencing analysis was employed to characterize mRNA expression profiles in female hearts. Results: Loss of miRNA-22 attenuated body weight gain, adiposity, and prevented obesogenic diet-induced insulin resistance and dyslipidemia in females. WT obese females developed cardiac hypertrophy. Interestingly, miRNA-22 KO females displayed cardiac hypertrophy without left ventricular dysfunction and myocardial fibrosis. Both miRNA-22 deletion and obesogenic diet changed mRNA expression profiles in female hearts. Enrichment analysis revealed that genes associated with regulation of the force of heart contraction, protein folding and fatty acid oxidation were enriched in hearts of WT obese females. In addition, genes related to thyroid hormone responses, heart growth and PI3K signaling were enriched in hearts of miRNA-22 KO females. Interestingly, miRNA-22 KO obese females exhibited reduced mRNA levels of Yap1, Egfr and Tgfbr1 compared to their respective controls. Conclusion: This study reveals that miRNA-22 deletion induces cardiac hypertrophy in females without affecting myocardial function. In addition, our findings suggest miRNA-22 as a potential therapeutic target to treat obesity-related metabolic disorders in females.

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