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

Cells ◽  
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.

scholarly journals Gestational Diabetes Mellitus and Infant Adiposity at Birth: A Systematic Review and Meta-Analysis of Therapeutic Interventions

2021 ◽  
Vol 10 (4) ◽  
pp. 835
Author(s):  
Manoja P. Herath ◽  
Jeffrey M. Beckett ◽  
Andrew P. Hills ◽  
Nuala M. Byrne ◽  
Kiran D. K. Ahuja
Keyword(s):  
Diabetes Mellitus ◽  
Adipose Tissue ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Fat Mass ◽  
Metabolic Disorders ◽  
Later Life ◽  
Therapeutic Interventions ◽  
Increased Risk ◽  
The Impact

Exposure to untreated gestational diabetes mellitus (GDM) in utero increases the risk of obesity and type 2 diabetes in adulthood, and increased adiposity in GDM-exposed infants is suggested as a plausible mediator of this increased risk of later-life metabolic disorders. Evidence is equivocal regarding the impact of good glycaemic control in GDM mothers on infant adiposity at birth. We systematically reviewed studies reporting fat mass (FM), percent fat mass (%FM) and skinfold thicknesses (SFT) at birth in infants of mothers with GDM controlled with therapeutic interventions (IGDMtr). While treating GDM lowered FM in newborns compared to no treatment, there was no difference in FM and SFT according to the type of treatment (insulin, metformin, glyburide). IGDMtr had higher overall adiposity (mean difference, 95% confidence interval) measured with FM (68.46 g, 29.91 to 107.01) and %FM (1.98%, 0.54 to 3.42) but similar subcutaneous adiposity measured with SFT, compared to infants exposed to normal glucose tolerance (INGT). This suggests that IGDMtr may be characterised by excess fat accrual in internal adipose tissue. Given that intra-abdominal adiposity is a major risk factor for metabolic disorders, future studies should distinguish adipose tissue distribution of IGDMtr and INGT.

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

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jessica G. Wallace ◽  
Christian J. Bellissimo ◽  
Erica Yeo ◽  
Yu Fei Xia ◽  
Jim J. Petrik ◽  
...  
Keyword(s):  
Structural Changes ◽  
Maternal Obesity ◽  
Intestinal Inflammation ◽  
Maternal Diet ◽  
Cell Number ◽  
Amino Acid Transporters ◽  
Metabolic Dysfunction ◽  
Transcript Levels ◽  
Increased Risk ◽  
Placental Inflammation

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.

scholarly journals The Impact of Maternal High-Fat Diet on Bone Microarchitecture in Offspring

2021 ◽  
Vol 8 ◽  
Author(s):  
Emma J. Buckels ◽  
Scott M. Bolam ◽  
Mei Lin Tay ◽  
Brya G. Matthews
Keyword(s):  
Bone Health ◽  
High Fat Diet ◽  
Maternal Obesity ◽  
Bone Microarchitecture ◽  
Later Life ◽  
Reproductive Age ◽  
High Fat ◽  
Increased Risk ◽  
Increase Fracture Risk ◽  
The Impact

The incidence of obesity in women of reproductive age has significantly increased over the past 100 years. There is a well-established connection between maternal obesity during pregnancy and an increased risk of developing non-communicable cardiometabolic diseases in her offspring. This mini-review focuses on evidence examining the effect of maternal high-fat diet (HFD) on skeletal development and bone health in later life in offspring. The majority of rodent studies indicate that maternal HFD generally negatively affects both embryonic bone development and bone volume in adult animals. Details surrounding the mechanisms of action that drive changes in the skeleton in offspring remain unclear, although numerous studies suggest that some effects are sex-specific. Human studies in this area are limited but also suggest that HFD during pregnancy may impair bone formation and increase fracture risk during childhood. Given the consequences of low bone mass and deranged bone microarchitecture for offspring, advances in our understanding of the developmental origins of bone health is critical in the battle against osteoporosis.

scholarly journals Developmental Programming of Nonalcoholic Fatty Liver Disease: The Effect of Early Life Nutrition on Susceptibility and Disease Severity in Later Life

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Minglan Li ◽  
Clare M. Reynolds ◽  
Stephanie A. Segovia ◽  
Clint Gray ◽  
Mark H. Vickers
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Early Life ◽  
Fatty Liver Disease ◽  
Maternal Obesity ◽  
Later Life ◽  
Developmental Programming ◽  
Nonalcoholic Fatty Liver ◽  
Increased Risk

Nonalcoholic fatty liver disease (NAFLD) is fast becoming the most common liver disease globally and parallels rising obesity rates. The developmental origins of health and disease hypothesis have linked alterations in the early life environment to an increased risk of metabolic disorders in later life. Altered early life nutrition, in addition to increasing risk for the development of obesity, type 2 diabetes, and cardiovascular disease in offspring, is now associated with an increased risk for the development of NAFLD. This review summarizes emerging research on the developmental programming of NAFLD by both maternal obesity and undernutrition with a particular focus on the possible mechanisms underlying the development of hepatic dysfunction and potential strategies for intervention.

The Effect of Exercise and Distraction on Blood Pressure Recovery Following an Anger-Provoking Stressor in Normotensive Young Adults

2015 ◽  
Vol 29 (2) ◽  
pp. 45-54 ◽  
Author(s):  
Faye S. Routledge ◽  
Judith A. McFetridge-Durdle ◽  
Marilyn Macdonald ◽  
Lynn Breau ◽  
Tavis Campbell
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Health ◽  
Exercise Intervention ◽  
Recovery Period ◽  
Intervention Group ◽  
Exercise Group ◽  
State Anger ◽  
Increased Risk ◽  
Anger Reactivity ◽  
Quiet Sitting

Ruminating about a prior anger provoking event is found to elevate blood pressure (BP) and delay BP recovery. Delayed BP recovery may be associated with increased risk of hypertension. Interventions that improve BP recovery may be beneficial for cardiovascular health. The purposes of this study were to evaluate the influence of rumination and anger on BP reactivity and recovery, to compare the effect of an exercise intervention or distraction intervention on BP recovery and to explore if exercise improved BP recovery by distracting participants from stressor-related rumination and anger. Healthy, normotensive participants (n = 79, mean age 22.2 ± 4.0 years) underwent an anger-recall interview stressor task, 3 min of exercise (walking), distraction (reading) or no-intervention (quiet sitting) and a 15 min recovery period. State anger reactivity was associated with Δ diastolic (D) BP reactivity and approached significance with Δ systolic (S) BP reactivity. Trait rumination was associated with greater SBP during recovery. Δ SBP recovery did not differ between the exercise, distraction and no-intervention groups. Although there were no differences in Δ DBP recovery between the exercise and no-intervention groups, distraction improved Δ DBP recovery compared to the exercise intervention but not the no-intervention. The proportion of anger-related thoughts (state rumination) in the exercise group did not differ from the distraction or no-intervention groups. However, a smaller proportion of participants in the distraction intervention reported an anger-related thought during recovery compared to the no-intervention group with 76% of their thoughts relating to the provided distraction. Overall, post-stressor exercise was not found to improve BP recovery while reading was effective at distracting individuals from angry thoughts (state rumination) but had no effect on BP compared to no-intervention.

Effects of Maternal Obesity and Gestational Diabetes Mellitus on the Placenta: Current Knowledge and Targets for Therapeutic Interventions

2020 ◽  
Vol 19 (2) ◽  
pp. 176-192
Author(s):  
Samantha Bedell ◽  
Janine Hutson ◽  
Barbra de Vrijer ◽  
Genevieve Eastabrook
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Maternal Obesity ◽  
Environmental Changes ◽  
Current Knowledge ◽  
Therapeutic Interventions ◽  
Placental Development ◽  
Exchange Site ◽  
And Function

: Obesity and gestational diabetes mellitus (GDM) are becoming more common among pregnant women worldwide and are individually associated with a number of placenta-mediated obstetric complications, including preeclampsia, macrosomia, intrauterine growth restriction and stillbirth. The placenta serves several functions throughout pregnancy and is the main exchange site for the transfer of nutrients and gas from mother to fetus. In pregnancies complicated by maternal obesity or GDM, the placenta is exposed to environmental changes, such as increased inflammation and oxidative stress, dyslipidemia, and altered hormone levels. These changes can affect placental development and function and lead to abnormal fetal growth and development as well as metabolic and cardiovascular abnormalities in the offspring. This review aims to summarize current knowledge on the effects of obesity and GDM on placental development and function. Understanding these processes is key in developing therapeutic interventions with the goal of mitigating these effects and preventing future cardiovascular and metabolic pathology in subsequent generations.

The Need for Personalized Risk-Stratified Approaches to Treatment for Gestational Diabetes: A Narrative Review

2021 ◽  
Author(s):  
Shamil D. Cooray ◽  
Jacqueline A. Boyle ◽  
Georgia Soldatos ◽  
Shakila Thangaratinam ◽  
Helena J. Teede
Keyword(s):  
Gestational Diabetes ◽  
Pregnancy Outcomes ◽  
Population Based ◽  
Adverse Pregnancy Outcomes ◽  
Therapeutic Interventions ◽  
Clinical Prediction Model ◽  
Increased Risk ◽  
Adverse Pregnancy ◽  
The Individual ◽  
Personalized Risk

AbstractGestational diabetes mellitus (GDM) is common and is associated with an increased risk of adverse pregnancy outcomes. However, the prevailing one-size-fits-all approach that treats all women with GDM as having equivalent risk needs revision, given the clinical heterogeneity of GDM, the limitations of a population-based approach to risk, and the need to move beyond a glucocentric focus to address other intersecting risk factors. To address these challenges, we propose using a clinical prediction model for adverse pregnancy outcomes to guide risk-stratified approaches to treatment tailored to the individual needs of women with GDM. This will allow preventative and therapeutic interventions to be delivered to those who will maximally benefit, sparing expense, and harm for those at a lower risk.

scholarly journals Long term alterations of growth after antenatal steroids in preterm twin pregnancies

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Thorsten Braun ◽  
Vivien Filleböck ◽  
Boris Metze ◽  
Christoph Bührer ◽  
Andreas Plagemann ◽  
...  
Keyword(s):  
Early Childhood ◽  
Disease Risk ◽  
Later Life ◽  
Ponderal Index ◽  
Childhood Growth ◽  
Antenatal Steroids ◽  
Increased Risk ◽  
Infancy And Early Childhood ◽  
Twin Pregnancies

AbstractObjectivesTo compare the long-term effects of antenatal betamethasone (ANS, ≤16 mg, =24 mg and >24 mg) in twins on infant and childhood growth.MethodsA retrospective cohort follow up study among 198 twins after ANS including three time points: U1 first neonatal examination after birth and in the neonatal period; U7 examination from the 21st to the 24th month of life and U9 examination from the 60th to the 64th month of life using data from copies of the children’s examination booklets. Inclusion criteria are twin pregnancies with preterm labor, cervical shortening, preterm premature rupture of membranes, or vaginal bleeding, and exposure to ANS between 23+5 and 33+6 weeks. Outcome measures are dosage-dependent and sex-specific effects of ANS on growth (body weight, body length, head circumference, body mass index and ponderal index) up to 5.3 years.ResultsOverall, 99 live-born twin pairs were included. Negative effects of ANS on fetal growth persisted beyond birth, altered infant and childhood growth, independent of possible confounding factors. Overall weight percentile significantly decreased between infancy and early childhood by 18.8%. Birth weight percentiles significantly changed in a dose dependent and sex specific manner, most obviously in female-female and mixed pairs. The ponderal index significantly decreased up to 42.9%, BMI index increased by up to 33.8%.ConclusionsANS results in long-term alterations in infant and childhood growth. Changes between infancy and early childhood in ponderal mass index and BMI, independent of dose or twin pair structure, might indicate an ANS associated increased risk for later life disease.SynopsisFirst-time report on long-term ANS administration growth effects in twin pregnancies, showing persisting alterations beyond birth in infant and childhood growth up to 5.3 years as potential indicator of later life disease risk.

scholarly journals Psychosocial interventions to support the mental health of informal caregivers of persons living with dementia – a systematic literature review

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Henrik Wiegelmann ◽  
Sarah Speller ◽  
Lisa-Marie Verhaert ◽  
Liane Schirra-Weirich ◽  
Karin Wolf-Ostermann
Keyword(s):  
Mental Health ◽  
Informal Caregivers ◽  
Psychosocial Interventions ◽  
Health Interventions ◽  
Subjective Burden ◽  
Dementia Caregivers ◽  
Targeted Interventions ◽  
Positive Effects ◽  
Increased Risk ◽  
Mental Health Interventions

Abstract Background Informal caregivers of persons living with dementia have an increased risk of adverse mental health effects. It is therefore important to systematically summarize published literature in order to find out which mental health interventions generate effective support for informal caregivers of persons living with dementia. The objective of this study is to conduct a systematic review of intervention content, effectiveness and subgroup differentiation of mental health interventions for informal caregivers of persons with dementia living at home. Method We searched four electronic databases (PubMed, PsychINFO, Scopus and CINAHL) and included only methodically high-quality randomized controlled trials (RCTs), published in English or German language between 2009 and 2018. The intervention programmes focused on mental health of family caregivers. A narrative synthesis of the included studies is given. Results Forty-eight publications relating to 46 intervention programmes met the inclusion criteria. Burden, depression and quality of life (QoL) are the predominant parameters that were investigated. Twenty-five of forty-six interventions (54.3%) show positive effects on at least one of the outcomes examined. Most often, positive effects are reported for the outcome subjective burden (46.2%). Only six studies explicitly target on a certain subgroup of informal dementia caregivers (13%), whereas all other interventions (87%) target the group as a whole without differentiation. Conclusion The most beneficial results were found for cognitive behavioural approaches, especially concerning the reduction of depressive symptoms. Besides this, leisure and physical activity interventions show some good results in reducing subjective caregiver burden. In order to improve effectiveness, research and practice may focus on developing more targeted interventions for special dementia informal caregiver subgroups.

scholarly journals Cancer-Associated Fibroblasts as Players in Cancer Development and Progression and Their Role in Targeted Radionuclide Imaging and Therapy

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1100
Author(s):  
Sofia Koustoulidou ◽  
Mark W. H. Hoorens ◽  
Simone U. Dalm ◽  
Shweta Mahajan ◽  
Reno Debets ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Tumour Microenvironment ◽  
Therapeutic Interventions ◽  
Great Promise ◽  
Cancer Associated Fibroblasts ◽  
Functional Heterogeneity ◽  
Radioligand Therapy ◽  
Targeted Interventions ◽  
Theranostic Applications ◽  
Complex Origin

Cancer Associated Fibroblasts (CAFs) form a major component of the tumour microenvironment, they have a complex origin and execute diverse functions in tumour development and progression. As such, CAFs constitute an attractive target for novel therapeutic interventions that will aid both diagnosis and treatment of various cancers. There are, however, a few limitations in reaching successful translation of CAF targeted interventions from bench to bedside. Several approaches targeting CAFs have been investigated so far and a few CAF-targeting tracers have successfully been developed and applied. This includes tracers targeting Fibroblast Activation Protein (FAP) on CAFs. A number of FAP-targeting tracers have shown great promise in the clinic. In this review, we summarize our current knowledge of the functional heterogeneity and biology of CAFs in cancer. Moreover, we highlight the latest developments towards theranostic applications that will help tumour characterization, radioligand therapy and staging in cancers with a distinct CAF population.

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