High Fat Diet and In Utero Exposure to Maternal Obesity Disrupts Circadian Rhythm and Leads to Metabolic Programming of Liver in Rat Offspring

The proportion of pregnant women who are obese at conception continues to rise. Compelling evidence suggests the intrauterine environment is an important determinant of offspring health. Maternal obesity and unhealthy diets are shown to promote metabolic programming in the offspring. Mitochondria are maternally inherited, and we have previously shown impaired mitochondrial function in rat offspring exposed to maternal obesity in utero. Mitochondrial health is maintained by mitochondrial dynamics, or the processes of fusion and fission, which serve to repair damaged mitochondria, remove irreparable mitochondria, and maintain mitochondrial morphology. An imbalance between fusion and fission has been associated with obesity, insulin resistance, and reproduction complications. In the present study, we examined the influence of maternal obesity and postweaning high-fat diet (HFD) on key regulators of mitochondrial fusion and fission in rat offspring at important developmental milestones which included postnatal day (PND)35 (2 wk HFD) and PND130 (∼16 wk HFD). Our results indicate HFD-fed offspring had reduced mRNA expression of presenilin-associated rhomboid-like (PARL), optic atrophy (OPA)1, mitofusin (Mfn)1, Mfn2, fission (Fis)1, and nuclear respiratory factor (Nrf)1 at PND35, while OPA1 and Mfn2 remained decreased at PND130. Putative transcriptional regulators of mitochondrial dynamics were reduced in rat placenta and offspring liver and skeletal muscle [peroxisome proliferator-activated receptor gamma coactivator (PGC1)α, PGC1β, and estrogen-related receptor (ERR)α], consistent with indirect calorimetry findings revealing reduced energy expenditure and impaired fat utilization. Overall, maternal obesity detrimentally alters mitochondrial targets that may contribute to impaired mitochondrial health and increased obesity susceptibility in later life.

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Maternal obesity and post‐natal high fat diet disrupt hepatic circadian rhythm in rat offspring

The FASEB Journal ◽

10.1096/fasebj.27.1_supplement.1081.2 ◽

2013 ◽

Vol 27 (S1) ◽

Author(s):

Kartik Shankar ◽

Sarah J Borengasser ◽

Jennifer Faske ◽

Ping Kang ◽

Horacio Gomez‐Acevedo

Keyword(s):

Circadian Rhythm ◽

High Fat Diet ◽

Maternal Obesity ◽

High Fat ◽

Rat Offspring

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64: In utero exposure to a maternal high fat diet Alters the epigenetic histone code in a murine model

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2013.10.097 ◽

2014 ◽

Vol 210 (1) ◽

pp. S42-S43

Author(s):

Melissa Suter ◽

Jun Ma ◽

Patricia Vuguin ◽

Kirsten Hartil ◽

Ariana Fiallo ◽

...

Keyword(s):

Murine Model ◽

High Fat Diet ◽

In Utero ◽

Histone Code ◽

In Utero Exposure ◽

High Fat

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Maternal high-fat diet induces sex-specific changes to glucocorticoid and inflammatory signaling in response to corticosterone and lipopolysaccharide challenge in adult rat offspring

10.1101/780783 ◽

2019 ◽

Author(s):

Sanoji Wijenayake ◽

Mouly F. Rahman ◽

Christine M.W. Lum ◽

Wilfred C. De Vega ◽

Aya Sasaki ◽

...

Keyword(s):

Gene Expression ◽

High Fat Diet ◽

Maternal Obesity ◽

Inflammatory Responses ◽

Physiological Stress ◽

High Fat ◽

Inflammatory Gene Expression ◽

Inflammatory Genes ◽

Inflammatory Gene ◽

Rat Offspring

ABSTRACTBackgroundAcute elevations in endogenous corticosterone (CORT) with psychosocial stress or exogenous administration potentiate inflammatory gene expression. Maternal obesity as a result of high-fat diet (HFD) consumption has been linked to higher basal levels of neuroinflammation, including increased expression of pro-inflammatory genes in the amygdala. These findings suggest that exposure to maternal HFD may elicit pro-inflammatory responses in the presence of an immune stressor such as lipopolysaccharide (LPS), a component of gram-negative bacteria, as well as acute elevated CORT.MethodsRat offspring were exposed to maternal HFD or control diet (CHD) throughout pre and postnatal development until weaning, when all offspring were provided CHD until adulthood. In adulthood, offspring were ‘challenged’ with administration of exogenous CORT, to simulate an acute physiological stress, LPS, to induce an immune stress, or both. qPCR was used to measure transcript abundance of CORT receptors and downstream inflammatory genes in the amygdala, hippocampus and prefrontal cortex, brain regions that mediate neuroendocrine and behavioral responses to stress.ResultsHFD female offspring exhibited elevations in anti-inflammatory transcripts, whereas HFD male offspring responded with greater pro-inflammatory gene expression to simultaneous CORT and LPS administration.ConclusionsThese findings suggest that exposure to maternal HFD leads to sex-specific alterations that may alter inflammatory responses in the brain, possibly as an adaptive response to basal inflammation.

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53: In utero exposure to a maternal high fat diet alters the epigenetic histone code in a murine model

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2009.10.068 ◽

2009 ◽

Vol 201 (6) ◽

pp. S31

Author(s):

Melissa Suter ◽

Kirsten Hartil ◽

Patricia Vuguin ◽

Ariana Fiallo ◽

Maureen Charron ◽

...

Keyword(s):

Murine Model ◽

High Fat Diet ◽

In Utero ◽

Histone Code ◽

In Utero Exposure ◽

High Fat

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In utero exposure to germinated brown rice and its oryzanol-rich extract attenuated high fat diet-induced insulin resistance in F1 generation of rats

BMC Complementary and Alternative Medicine ◽

10.1186/s12906-017-1571-0 ◽

2017 ◽

Vol 17 (1) ◽

Cited By ~ 5

Author(s):

Hadiza Altine Adamu ◽

Mustapha Umar Imam ◽

Der-Jiun Ooi ◽

Norhaizan Mohd Esa ◽

Rozita Rosli ◽

...

Keyword(s):

Insulin Resistance ◽

High Fat Diet ◽

Brown Rice ◽

In Utero ◽

In Utero Exposure ◽

High Fat ◽

Germinated Brown Rice ◽

F1 Generation

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Alteration of the Early Development Environment by Maternal Diet and the Occurrence of Autistic-like Phenotypes in Rat Offspring

International Journal of Molecular Sciences ◽

10.3390/ijms22189662 ◽

2021 ◽

Vol 22 (18) ◽

pp. 9662

Author(s):

Kinga Gawlińska ◽

Dawid Gawliński ◽

Ewelina Kowal-Wiśniewska ◽

Małgorzata Jarmuż-Szymczak ◽

Małgorzata Filip

Keyword(s):

High Fat Diet ◽

Maternal Obesity ◽

Maternal Diet ◽

Repetitive Behavior ◽

Autism Spectrum ◽

High Fat ◽

Development Environment ◽

Rat Offspring ◽

Adolescent Offspring ◽

Pregnancy And Lactation

Epidemiological and preclinical studies suggest that maternal obesity increases the risk of autism spectrum disorder (ASD) in offspring. Here, we assessed the effects of exposure to modified maternal diets limited to pregnancy and lactation on brain development and behavior in rat offspring of both sexes. Among the studied diets, a maternal high-fat diet (HFD) disturbed the expression of ASD-related genes (Cacna1d, Nlgn3, and Shank1) and proteins (SHANK1 and TAOK2) in the prefrontal cortex of male offspring during adolescence. In addition, a maternal high-fat diet induced epigenetic changes by increasing cortical global DNA methylation and the expression of miR-423 and miR-494. As well as the molecular changes, behavioral studies have shown male-specific disturbances in social interaction and an increase in repetitive behavior during adolescence. Most of the observed changes disappeared in adulthood. In conclusion, we demonstrated the contribution of a maternal HFD to the predisposition to an ASD-like phenotype in male adolescent offspring, while a protective effect occurred in females.

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In utero exposure to a maternal high-fat diet alters the epigenetic histone code in a murine model

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2014.01.045 ◽

2014 ◽

Vol 210 (5) ◽

pp. 463.e1-463.e11 ◽

Cited By ~ 30

Author(s):

Melissa A. Suter ◽

Jun Ma ◽

Patricia M. Vuguin ◽

Kirsten Hartil ◽

Ariana Fiallo ◽

...

Keyword(s):

Murine Model ◽

High Fat Diet ◽

In Utero ◽

Histone Code ◽

In Utero Exposure ◽

High Fat

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Maternal high-fat diet induces long-term obesity with sex-dependent metabolic programming of adipocyte differentiation, hypertrophy and dysfunction in the offspring

Clinical Science ◽

10.1042/cs20191229 ◽

2020 ◽

Vol 134 (7) ◽

pp. 921-939 ◽

Cited By ~ 6

Author(s):

Thorsten Litzenburger ◽

Eva-Kristina Huber ◽

Katharina Dinger ◽

Rebecca Wilke ◽

Christina Vohlen ◽

...

Keyword(s):

Inflammatory Response ◽

High Fat Diet ◽

Early Phase ◽

Molecular Mechanisms ◽

Maternal Obesity ◽

Late Phase ◽

Metabolic Programming ◽

Dependent Manner ◽

Adipocyte Size ◽

High Fat

Abstract Maternal obesity determines obesity and metabolic diseases in the offspring. The white adipose tissue (WAT) orchestrates metabolic pathways, and its dysfunction contributes to metabolic disorders in a sex-dependent manner. Here, we tested if sex differences influence the molecular mechanisms of metabolic programming of WAT in offspring of obese dams. To this end, maternal obesity was induced with high-fat diet (HFD) and the offspring were studied at an early phase [postnatal day 21 (P21)], a late phase (P70) and finally P120. In the early phase we found a sex-independent increase in WAT in offspring of obese dams using magnetic resonance imaging (MRI), which was more pronounced in females than males. While the adipocyte size increased in both sexes, the distribution of WAT differed in males and females. As mechanistic hints, we identified an inflammatory response in females and a senescence-associated reduction in the preadipocyte factor DLK in males. In the late phase, the obese body composition persisted in both sexes, with a partial reversal in females. Moreover, female offspring recovered completely from both the adipocyte hypertrophy and the inflammatory response. These findings were linked to a dysregulation of lipolytic, adipogenic and stemness-related markers as well as AMPKα and Akt signaling. Finally, the sex-dependent metabolic programming persisted with sex-specific differences in adipocyte size until P120. In conclusion, we do not only provide new insights into the molecular mechanisms of sex-dependent metabolic programming of WAT dysfunction, but also highlight the sex-dependent development of low- and high-grade pathogenic obesity.

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