Neonatal streptozotocin-induced diabetes in mothers promotes metabolic programming of adipose tissue in male rat offspring

2022

IJMS

Metabolic syndrome (MetS) is an extremely prevalent complex trait and it can originate in early life. This concept is now being termed the developmental origins of health and disease (DOHaD). Increasing evidence supports that disturbance of gut microbiota influences various risk factors of MetS. The DOHaD theory provides an innovative strategy to prevent MetS through early intervention (i.e., reprogramming). In this review, we summarize the existing literature that supports how environmental cues induced MetS of developmental origins and the interplay between gut microbiota and other fundamental underlying mechanisms. We also present an overview of experimental animal models addressing implementation of gut microbiota-targeted reprogramming interventions to avert the programming of MetS. Even with growing evidence from animal studies supporting the uses of gut microbiota-targeted therapies start before birth to protect against MetS of developmental origins, their effects on pregnant women are still unknown and these results require further clinical translation.

Section: Current Evidence Supports Mets Of Developmental Originsmentioning

confidence: 99%

Maternal Supplementation of Probiotics, Prebiotics or Postbiotics to Prevent Offspring Metabolic Syndrome: The Gap between Preclinical Results and Clinical Translation

Huang

Tain

2022

IJMS

“…In the model of uteroplacental insufficiency developed by uterine artery ligation in the pregnant rat, IUGR offspring developed hypertension, dyslipidemia and insulin resistance in adulthood [50,51]. Additionally, several animal models resembling maternal conditions and diseases have been evaluated, such as polycystic ovary syndrome (PCOS) [52,53], maternal hypoxia [52,54], maternal inflammation [55,56], diabetes [57][58][59], and chronodisruption [60,61].…”

Section: Maternal Illnesses and Conditionsmentioning

confidence: 99%

“…It is clear from a range of human observational studies that maternal diabetes gives rise to different phenotypes of MetS in offspring, including obesity, insulin resistance, hypertension, dyslipidemia, and CVDs [85]. The majority of rodent studies of maternal diabetes have employed streptozotocin (STZ)-induced diabetes [57][58][59]. When injected into neonates [57,58] or adult rats [57,59], STZ can cause type 1 or type 2 diabetes, respectively.…”

Section: Maternal Illnesses and Conditionsmentioning

confidence: 99%

“…The majority of rodent studies of maternal diabetes have employed streptozotocin (STZ)-induced diabetes [57][58][59]. When injected into neonates [57,58] or adult rats [57,59], STZ can cause type 1 or type 2 diabetes, respectively. Almost all major characteristics of MetS are present in adult offspring born to diabetic mothers at 12-16 weeks of age [57][58][59], which are largely in line with the findings in humans.…”

Section: Maternal Illnesses and Conditionsmentioning

confidence: 99%

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Early-Life Origins of Metabolic Syndrome: Mechanisms and Preventive Aspects

Hou

et al. 2021

IJMS

One of the leading global public-health burdens is metabolic syndrome (MetS), despite the many advances in pharmacotherapies. MetS, now known as “developmental origins of health and disease” (DOHaD), can have its origins in early life. Offspring MetS can be programmed by various adverse early-life conditions, such as nutrition imbalance, maternal conditions or diseases, maternal chemical exposure, and medication use. Conversely, early interventions have shown potential to revoke programming processes to prevent MetS of developmental origins, namely reprogramming. In this review, we summarize what is currently known about adverse environmental insults implicated in MetS of developmental origins, including the fundamental underlying mechanisms. We also describe animal models that have been developed to study the developmental programming of MetS. This review extends previous research reviews by addressing implementation of reprogramming strategies to prevent the programming of MetS. These mechanism-targeted strategies include antioxidants, melatonin, resveratrol, probiotics/prebiotics, and amino acids. Much work remains to be accomplished to determine the insults that could induce MetS, to identify the mechanisms behind MetS programming, and to develop potential reprogramming strategies for clinical translation.

“…Indeed, Glut4 expression is specifically decreased in the muscle of female rats exposed to a maternal undernutrition or low-protein diet during gestation [ 60 , 94 ]. However, GLUT4 abundance is decreased in the muscle of male rats from diabetic dams but increased in the adipose tissue [ 139 , 141 , 142 ]. The abundance of the insulin-independent glucose transporter, GLUT1 is increased in the skeletal muscle of offspring in response to maternal undernutrition or uterine ligation [ 60 , 118 ].…”

Section: Adipose and Skeletal Muscle Glucose Uptakementioning

confidence: 99%

Molecular mechanisms governing offspring metabolic programming in rodent models of in utero stress

Christoforou

Sferruzzi‐Perri

2020

Cell. Mol. Life Sci.

The results of different human epidemiological datasets provided the impetus to introduce the now commonly accepted theory coined as 'developmental programming', whereby the presence of a stressor during gestation predisposes the growing fetus to develop diseases, such as metabolic dysfunction in later postnatal life. However, in a clinical setting, human lifespan and inaccessibility to tissue for analysis are major limitations to study the molecular mechanisms governing developmental programming. Subsequently, studies using animal models have proved indispensable to the identification of key molecular pathways and epigenetic mechanisms that are dysregulated in metabolic organs of the fetus and adult programmed due to an adverse gestational environment. Rodents such as mice and rats are the most used experimental animals in the study of developmental programming. This review summarises the molecular pathways and epigenetic mechanisms influencing alterations in metabolic tissues of rodent offspring exposed to in utero stress and subsequently programmed for metabolic dysfunction. By comparing molecular mechanisms in a variety of rodent models of in utero stress, we hope to summarise common themes and pathways governing later metabolic dysfunction in the offspring whilst identifying reasons for incongruencies between models so to inform future work. With the continued use and refinement of such models of developmental programming, the scientific community may gain the knowledge required for the targeted treatment of metabolic diseases that have intrauterine origins.