Obesity during pregnancy results in maternal intestinal inflammation, placental hypoxia, and alters fetal glucose metabolism at mid-gestation

AbstractWe investigated whether diet-induced changes in the maternal intestinal microbiota were associated with changes in bacterial metabolites and their receptors, intestinal inflammation, and placental inflammation at mid-gestation (E14.5) in female mice fed a control (17% kcal fat, n = 7) or a high-fat diet (HFD 60% kcal fat, n = 9; ad libitum) before and during pregnancy. Maternal diet-induced obesity (mDIO) resulted in a reduction in maternal fecal short-chain fatty acid producing Lachnospiraceae, lower cecal butyrate, intestinal antimicrobial peptide levels, and intestinal SCFA receptor Ffar3, Ffar2 and Hcar2 transcript levels. mDIO increased maternal intestinal pro-inflammatory NFκB activity, colonic CD3+ T cell number, and placental inflammation. Maternal obesity was associated with placental hypoxia, increased angiogenesis, and increased transcript levels of glucose and amino acid transporters. Maternal and fetal markers of gluconeogenic capacity were decreased in pregnancies complicated by obesity. We show that mDIO impairs bacterial metabolite signaling pathways in the mother at mid-gestation, which was associated with significant structural changes in placental blood vessels, likely as a result of placental hypoxia. It is likely that maternal intestinal changes contribute to adverse maternal and placental adaptations that, via alterations in fetal hepatic glucose handling, may impart increased risk of metabolic dysfunction in offspring.

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Maternal Diet-induced Obesity Programs Cardiovascular Dysfunction in Adult Male Mouse Offspring Independent of Current Body Weight

Endocrinology ◽

10.1210/en.2014-1383 ◽

2014 ◽

Vol 155 (10) ◽

pp. 3970-3980 ◽

Cited By ~ 59

Author(s):

Heather L. Blackmore ◽

Youguo Niu ◽

Denise S. Fernandez-Twinn ◽

Jane L. Tarry-Adkins ◽

Dino A. Giussani ◽

...

Keyword(s):

Body Weight ◽

Maternal Obesity ◽

Maternal Diet ◽

Saturated Fat ◽

Premature Death ◽

Causal Link ◽

Cardiac Contraction ◽

Diet Induced Obesity ◽

Increased Risk ◽

Pregnancy And Lactation

Abstract Obese pregnancies are not only associated with adverse consequences for the mother but also the long-term health of her child. Human studies have shown that individuals from obese mothers are at increased risk of premature death from cardiovascular disease (CVD), but are unable to define causality. This study aimed to determine causality using a mouse model of maternal diet–induced obesity. Obesity was induced in female C57BL/6 mice by feeding a diet rich in simple sugars and saturated fat 6 weeks prior to pregnancy and throughout pregnancy and lactation. Control females were fed laboratory chow. Male offspring from both groups were weaned onto chow and studied at 3, 5, 8, and 12 weeks of age for gross cardiac morphometry using stereology, cardiomyocyte cell area by histology, and cardiac fetal gene expression using qRT-PCR. Cardiac function was assessed by isolated Langendorff technology at 12 weeks of age and hearts were analyzed at the protein level for the expression of the β1 adrenergic receptor, muscarinic type-2 acetylcholine receptor, and proteins involved in cardiac contraction. Offspring from obese mothers develop pathologic cardiac hypertrophy associated with re-expression of cardiac fetal genes. By young adulthood these offspring developed severe systolic and diastolic dysfunction and cardiac sympathetic dominance. Importantly, cardiac dysfunction occurred in the absence of any change in corresponding body weight and despite the offspring eating a healthy low-fat diet. These findings provide a causal link to explain human observations relating maternal obesity with premature death from CVD in her offspring.

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Deletion of mucin 2 induces colitis with concomitant metabolic abnormalities in mice

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00277.2020 ◽

2021 ◽

Author(s):

Jiayu Ye ◽

Natasha Haskey ◽

Hansika Dadlani ◽

Hatem M Zubaidi ◽

Jacqueline A Barnett ◽

...

Keyword(s):

Intestinal Inflammation ◽

Peroxisome Proliferator ◽

Metabolic Dysfunction ◽

Metabolic Abnormalities ◽

Knock Out ◽

Metabolism Regulation ◽

Increased Risk ◽

Mucin 2 ◽

The Impact ◽

Chronic Intestinal Inflammation

Patients with inflammatory bowel disease (IBD) are at increased risk for under recognized metabolic co-morbidities. Chronic intestinal inflammation in IBD along with changes to the gut microbiome leads to broader systemic effects. Despite the existence of multiple animal models to study colitis, limited studies have examined the metabolic abnormalities associated with these models. In this study, a spontaneous model of colitis (mucin 2 knock-out mouse, Muc2-/-) was used to investigate the impact of intestinal disease on metabolic dysfunction. Prior to onset of severe colitis, such as rectal prolapse, Muc2-/- mice exhibited impaired glucose clearance. Defects were noted in the insulin signaling pathway corresponding with upregulated genes in lipid utilization pathways, increased mitochondrial number and peroxisome proliferator-activated coactivator 1-alpha (PGC-1 alpha), a transcription factor central to energy metabolism regulation. Parallel to these metabolic alterations, Muc2-/- mice exhibited systemic inflammation and bacteremia. We further characterize the dysbiotic microbiome's predicted functional categories given its contributing role to the colitic phenotype in the Muc2-/- mice. In addition to less butyrate levels, we show an increased predisposition to lipid metabolism and lipid biosynthesis pathways in the microbiome associated with the host's altered metabolic state. This study establishes the Muc2-/- mouse model that develops spontaneous colitis, as an ideal model for studying early co-morbid metabolic dysfunction. Clarification of the underlying etiology of two phenotypes in this model could unravel important clues regarding the treatment of metabolic comorbidities during colitis.

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Maternal Exercise Mediates Hepatic Metabolic Programming via Activation of AMPK-PGC1α Axis in the Offspring of Obese Mothers

Cells ◽

10.3390/cells10051247 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1247

Author(s):

Philipp Kasper ◽

Saida Breuer ◽

Thorben Hoffmann ◽

Christina Vohlen ◽

Ruth Janoschek ◽

...

Keyword(s):

Hepatic Steatosis ◽

Maternal Obesity ◽

Exercise Intervention ◽

Wheel Running ◽

Later Life ◽

Therapeutic Interventions ◽

Metabolic Dysfunction ◽

Targeted Interventions ◽

Increased Risk ◽

Maternal Exercise

Maternal obesity is associated with an increased risk of hepatic metabolic dysfunction for both mother and offspring and targeted interventions to address this growing metabolic disease burden are urgently needed. This study investigates whether maternal exercise (ME) could reverse the detrimental effects of hepatic metabolic dysfunction in obese dams and their offspring while focusing on the AMP-activated protein kinase (AMPK), representing a key regulator of hepatic metabolism. In a mouse model of maternal western-style-diet (WSD)-induced obesity, we established an exercise intervention of voluntary wheel-running before and during pregnancy and analyzed its effects on hepatic energy metabolism during developmental organ programming. ME prevented WSD-induced hepatic steatosis in obese dams by alterations of key hepatic metabolic processes, including activation of hepatic ß-oxidation and inhibition of lipogenesis following increased AMPK and peroxisome-proliferator-activated-receptor-γ-coactivator-1α (PGC-1α)-signaling. Offspring of exercised dams exhibited a comparable hepatic metabolic signature to their mothers with increased AMPK-PGC1α-activity and beneficial changes in hepatic lipid metabolism and were protected from WSD-induced adipose tissue accumulation and hepatic steatosis in later life. In conclusion, this study demonstrates that ME provides a promising strategy to improve the metabolic health of both obese mothers and their offspring and highlights AMPK as a potential metabolic target for therapeutic interventions.

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EVALUATION OF LEFT VENTRICULAR MASS IN THE PREHYPERTENSIVES BY ELECTROCARDIOGRAPHY AND ECHOCARDIOGRAPHY

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2011.6.15 ◽

2011 ◽

pp. 119-125

Author(s):

Thi Thuy Hang Nguyen

Keyword(s):

Left Ventricular Hypertrophy ◽

Left Ventricular Mass ◽

Ventricular Hypertrophy ◽

Structural Changes ◽

Left Ventricular ◽

Control Group ◽

Concentric Left Ventricular Hypertrophy ◽

Increased Risk ◽

Lv Mass ◽

Left Ventricular Morphology

Objective: Prehypertensive individuals are at increased risk for developing hypertension and their complication. Many studies show that 2/3 prehypertensive individuals develop hypertension after 4 years. ECG and echocardiography are the routine tests used to assess LV mass. The objective of the research to determine the percentage of change in left ventricular morphology in the ECG, echocardiography, which explore the characteristics of left ventricular structural changes by echocardiography in pre-hypertensive subjects. Materials and method: We studied a total of 50 prehypertensive, 30 males (60%) and 20 females (40%), mean age 48.20±8.47years. 50 normotensive volunteers as control participants. These subjects were examined for ECG and echocardiography. Results: In prehypertensive group, with 18% of left ventricular hypertrophy on electrocardiogram, 12% of left ventricular hypertrophy on echocardiography; in the control group, we did not find any subjects with left ventricular hypertrophy. In the group with left ventricular hypertrophy, mostly eccentric left ventricular hypertrophy (83.33%), concentric left ventricular hypertrophy is 16.67%. Restructuring of left ventricular concentric for 15.9% of subjects without left ventricular hypertrophy on echocardiography. Conclusion: There have been changed in left ventricular morphology even in prehypertensive

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Cardiovascular Changes in Menopause

Current Cardiology Reviews ◽

10.2174/1573403x16666201106141811 ◽

2020 ◽

Vol 16 ◽

Author(s):

Anjana R Nair ◽

Aiswarya J Pillai ◽

Nandini Nair

Keyword(s):

Cardiovascular Risk ◽

Structural Changes ◽

Systemic Hypertension ◽

Metabolic Dysfunction ◽

Review Of Literature ◽

Coronary Anatomy ◽

Complex Interactions ◽

Fat Redistribution ◽

Current Therapies ◽

Cardiovascular Aging

: Menopause is associated with changes consistent with cardiovascular aging. The effects on cardiac disease is multifaceted affecting endothelial function, coronary artery physiology and metabolic dysfunction leading to structural changes in the coronary anatomy. A systematic review of literature from 1986 to 2019 was conducted using PubMed and Google Scholar. The search was directed to retrieve papers that addressed the changes in cardiovascular physiology in menopause and the current therapies available to treat cardiovascular manifestations of menopause. The metabolic and clinical factors secondary to menopause such as dyslipidemia, insulin resistance, fat redistribution and systemic hypertension contribute to the accelerated risk for cardiovascular aging and disease. Atherosclerosis appears to be the end result of the interaction between cardiovascular risk factors and their accentuation during the perimenopausal period. Additionally, complex interactions between oxidative stress and levels of L-arginine and ADMA may also influence endothelial dysfunction in menopause. The increased cardiovascular risk in menopause stems from the exaggerated effects of changing physiology on the cardiovascular system affecting peripheral, cardiac and cerebrovascular beds. The differential effects of menopause on cardiovascular disease at the subclinical, biochemical and molecular levels form the highlights of this review.

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Visuopathy of prematurity: is retinopathy just the tip of the iceberg?

Pediatric Research ◽

10.1038/s41390-021-01625-0 ◽

2021 ◽

Author(s):

Sigrid Hegna Ingvaldsen ◽

Tora Sund Morken ◽

Dordi Austeng ◽

Olaf Dammann

Keyword(s):

Visual Processing ◽

Structural Changes ◽

Developmental Trajectories ◽

Visual Pathway ◽

Visual Stream ◽

Visual Deficits ◽

Cortical Areas ◽

Cellular Architecture ◽

Increased Risk ◽

Dorsal Visual Stream

AbstractResearch on retinopathy of prematurity (ROP) focuses mainly on the abnormal vascularization patterns that are directly visible for ophthalmologists. However, recent findings indicate that children born prematurely also exhibit changes in the retinal cellular architecture and along the dorsal visual stream, such as structural changes between and within cortical areas. Moreover, perinatal sustained systemic inflammation (SSI) is associated with an increased risk for ROP and the visual deficits that follow. In this paper, we propose that ROP might just be the tip of an iceberg we call visuopathy of prematurity (VOP). The VOP paradigm comprises abnormal vascularization of the retina, alterations in retinal cellular architecture, choroidal degeneration, and abnormalities in the visual pathway, including cortical areas. Furthermore, VOP itself might influence the developmental trajectories of cerebral structures and functions deemed responsible for visual processing, thereby explaining visual deficits among children born preterm.

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Mechanisms Underlying the Cognitive and Behavioural Effects of Maternal Obesity

Nutrients ◽

10.3390/nu13010240 ◽

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.

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Ultrasonographic Evaluation of the Shoulders and Its Associations with Shoulder Pain, Age, and Swim Training in Masters Swimmers

Medicina ◽

10.3390/medicina57010029 ◽

2020 ◽

Vol 57 (1) ◽

pp. 29

Author(s):

Yuta Suzuki ◽

Noriaki Maeda ◽

Junpei Sasadai ◽

Kazuki Kaneda ◽

Taizan Shirakawa ◽

...

Keyword(s):

Rotator Cuff ◽

Shoulder Pain ◽

Structural Changes ◽

Partial Tear ◽

Increased Risk ◽

High Prevalence ◽

History Of ◽

Long Head ◽

Competitive Swimmers ◽

Rotator Cuff Tendinopathy

Background and objectives: The long head of the biceps (LHB) and rotator cuff tendinopathy is the major cause of shoulder pain in competitive swimmers. The risk of tendinopathy increases with aging; however, the structural changes of LHB and rotator cuff in populations of masters swimmers have not been well examined. The purpose of this study was to investigate the prevalence of ultrasonographic abnormalities of the shoulders in masters swimmers, and the association of pain, age, and swim training with structural changes in this population. Materials and Methods: A total of 60 subjects participated in this study, with 20 masters swimmers with shoulder pain, 20 asymptomatic masters swimmers, and 20 sex- and age-matched controls. All swimmers completed a self-reported questionnaire for shoulder pain, their history of competition, and training volume. Each subject underwent ultrasonographic examination of both shoulders for pathologic findings in the LHB tendon, rotator cuff (supraspinatus (SSP) and subscapularis (SSC)) tendons, and subacromial bursa (SAB) of both shoulders and had thickness measured. Results: The prevalence of tendinosis (LHB, 48.8%; SSP, 17.5%; SSC, 15.9%), partial tear (SSP, 35.0%), and calcification (SSC, 10.0%) were higher in swimmers than in controls. LHB and SSP tendinosis were associated with shoulder pain. Older age and later start of competition were associated with an increased risk of LHB tendinosis and SSC calcification. Earlier initiation of swimming and longer history of competition were associated with an increased risk of SSP and SSC tendinosis. The thicker SSP tendon significantly increased the risk of tendinosis and partial tear. Conclusions: A high prevalence of structural changes in the rotator cuff and biceps tendons in masters swimmers reflects the effect of shoulder symptoms, aging, and swim training.

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Social relations and self-rated health in a multi-ethnic social housing area undergoing demolition

European Journal of Public Health ◽

10.1093/eurpub/ckaa165.1004 ◽

2020 ◽

Vol 30 (Supplement_5) ◽

Author(s):

M F Kvorning ◽

A Srivarathan ◽

S Nygaard ◽

R Lund

Keyword(s):

Social Relations ◽

Social Housing ◽

Structural Changes ◽

Ethnically Diverse ◽

Political Agenda ◽

Residential Areas ◽

Self Rated Health ◽

Housing Area ◽

Increased Risk ◽

Contact Frequency

Abstract Background During the coming years, selected social housing areas in Denmark will undergo large structural changes as part of a political agenda. Previous studies on the effects of such interventions are inconclusive. Residential areas are important for the development of social relations and health. The aim of this study was to explore the associations between social relations and self-rated health (SRH) and the interaction with country of origin in an ethnically diverse social housing area undergoing demolition, and compare results with the municipality. Methods Data include multilingual interviewer driven surveys with residents aged 45+ years before demolition began in 2018 (N = 209) and during the demolition in 2019 (N = 132), and a health survey on municipality level (N = 1638). Information on social relations include contact frequency with and support from family, friends and neighbors. SRH was dichotomized into high/low. Descriptive and multivariate logistic regression analyses adjusted for age, sex and Western/non-Western origin are presented. Results In cross-sectional analyses from 2018, low contact frequency and low support increased the risk of low SRH, OR = 1.44 (0.63-3.29) and OR = 1.23 (0.62-2.48), especially when also having non-Western origin compared to having high contact frequency or support and Western origin, OR = 6.27 (1.80-21.84) and OR = 4.43 (1.68-11.69), respectively. The same association was seen in 2019 and on municipality level. Low contact frequency in 2018 was associated with higher risk of developing or maintaining low SRH in 2019 compared to the group with high contact frequency in 2018 in longitudinal analyses, OR = 3.04 (0.91-10.91). Conclusions Poor social relations increased the risk of low SRH, especially when also having non-Western origin. Having poor social relations before the demolition was associated with an increased risk of developing or maintaining low SRH during the demolition in an ethnically diverse social housing area. Key messages Having low contact frequency before area demolition in a social housing area in Denmark increased the risk of developing or maintaining low self-rated health after demolition had begun. Having poor social relations and non-Western origin is associated with a strong increased risk of low self-rated health in a deprived ethnic diverse social housing area in Denmark.

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Acute small intestinal inflammation results in persistent lymphatic alterations

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00340.2017 ◽

2018 ◽

Vol 314 (3) ◽

pp. G408-G417 ◽

Cited By ~ 6

Author(s):

Sonia Rehal ◽

Matthew Stephens ◽

Simon Roizes ◽

Shan Liao ◽

Pierre-Yves von der Weid

Keyword(s):

Dendritic Cell ◽

Lymphatic System ◽

Intestinal Inflammation ◽

Critical Role ◽

Lymphatic Vessels ◽

Lymphoid Tissues ◽

Functional Changes ◽

Increased Risk ◽

Small Intestinal ◽

Acute Ileitis

Inflammatory bowel disease (IBD) has a complex pathophysiology with limited treatments. Structural and functional changes in the intestinal lymphatic system have been associated with the disease, with increased risk of IBD occurrence linked to a history of acute intestinal injury. To examine the potential role of the lymphatic system in inflammation recurrence, we evaluated morphological and functional changes in mouse mucosal and mesenteric lymphatic vessels, and within the mesenteric lymph nodes during acute ileitis caused by a 7-day treatment with dextran sodium sulfate (DSS). We monitored whether the changes persisted during a 14-day recovery period and determined their potential consequences on dendritic cell (DC) trafficking between the mucosa and lymphoid tissues. DSS administration was associated with marked lymphatic abnormalities and dysfunctions exemplified by lymphangiectasia and lymphangiogenesis in the ileal mucosa and mesentery, increased mesenteric lymphatic vessel leakage, and lymphadenopathy. Lymphangiogenesis and lymphadenopathy were still evident after recovery from intestinal inflammation and correlated with higher numbers of DCs in mucosal and lymphatic tissues. Specifically, a deficit in CD103+ DCs observed during acute DSS in the lamina propria was reversed and further enhanced during recovery. We concluded that an acute intestinal insult caused alterations of the mesenteric lymphatic system, including lymphangiogenesis, which persisted after resolution of inflammation. These morphological and functional changes could compromise DC function and movement, increasing susceptibility to further gastrointestinal disease. Elucidation of the changes in mesenteric and intestinal lymphatic function should offer key insights for new therapeutic strategies in gastrointestinal disorders such as IBD. NEW & NOTEWORTHY Lymphatic integrity plays a critical role in small intestinal homeostasis. Acute intestinal insult in a mouse model of acute ileitis causes morphological and functional changes in mesenteric and intestinal lymphatic vessels. While some of the changes significantly regressed during inflammation resolution, others persisted, including lymphangiogenesis and altered dendritic cell function and movement, potentially increasing susceptibility to the recurrence of gastrointestinal inflammation.

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