Regulation of mouse hepatic genes in response to diet induced obesity, insulin resistance and fasting induced weight reduction

Raab, R. Michael; Bullen, John W.; Kelleher, Joanne K.; Mantzoros, Christos S.; Stephanopoulos, Gregory

doi:10.1186/1743-7075-2-15

Cited by 17 publications

(8 citation statements)

References 55 publications

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“…3, note that the overlap never reaches 14 orthogroups). Added shared genes in stickleback and mouse include BDNF (a candidate gene related to anxiety, stress and depression 32 ) and a regulator of G protein receptors RGS3 (related to insulin metabolism 33 ). We followed the same procedure for the unique genes and did not find any evidence of sharing between the two species.…”

Section: Resultsmentioning

confidence: 99%

Neurogenomic insights into paternal care and its relation to territorial aggression

et al. 2019

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Motherhood is characterized by dramatic changes in brain and behavior, but less is known about fatherhood. Here we report that male sticklebacks—a small fish in which fathers provide care—experience dramatic changes in neurogenomic state as they become fathers. Some genes are unique to different stages of paternal care, some genes are shared across stages, and some genes are added to the previously acquired neurogenomic state. Comparative genomic analysis suggests that some of these neurogenomic dynamics resemble changes associated with pregnancy and reproduction in mammalian mothers. Moreover, gene regulatory analysis identifies transcription factors that are regulated in opposite directions in response to a territorial challenge versus during paternal care. Altogether these results show that some of the molecular mechanisms of parental care might be deeply conserved and might not be sex-specific, and suggest that tradeoffs between opposing social behaviors are managed at the gene regulatory level.

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Section: Resultsmentioning

confidence: 99%

Neurogenomic insights into paternal care and its relation to territorial aggression

et al. 2019

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“…However, the major difference between intermittent fasting studies and our study protocol is that intermittent fasting is often associated with loss of bodyweight caused by a chronic caloric deficit (8). While weight loss is often the primary purpose of intermittent fasting, it represents a huge confounder when studying the possible memory effect of fasting (32,40). In addition, when fasting intermittently, the limited time between fasting episodes may not allow for a restoration of metabolic homeostasis, which is necessary to be able to detect a veritable memory effect.…”

Section: Discussionmentioning

confidence: 99%

Probing metabolic memory in the hepatic response to fasting

Defour

Hooiveld

Weeghel

et al. 2020

Physiological Genomics

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Tissues may respond differently to a particular stimulus if they have been previously exposed to that same stimulus. Here we tested the hypothesis that a strong metabolic stimulus such as fasting may influence the hepatic response to a subsequent fast and thus elicit a memory effect. Overnight fasting in mice significantly increased plasma free fatty acids, glycerol, β-hydroxybutyrate and liver triglycerides, and decreased plasma glucose, plasma triglycerides, and liver glycogen levels. In addition, fasting dramatically changed the liver transcriptome, upregulating genes involved in gluconeogenesis and in uptake, oxidation, storage, and mobilization of fatty acids, and downregulating genes involved in fatty acid synthesis, fatty acid elongation/desaturation, and cholesterol synthesis. Fasting also markedly impacted the liver metabolome, causing a decrease in the levels of numerous amino acids, glycolytic intermediated, TCA cycle intermediates, and nucleotides. However, these fasting-induced changes were unaffected by two previous overnight fasts. Also, no significant effect was observed of prior fasting on glucose tolerance. Finally, analysis of the effect of fasting on the transcriptome in hepatocyte humanized mouse livers indicated modest similarity in gene regulation in mouse and human liver cells. In general, genes involved in metabolic pathways were up- or downregulated to a lesser extent in human liver cells than mouse liver cells. In conclusion, we found that previous exposure to fasting in mice did not influence the hepatic response to a subsequent fast, arguing against the concept of metabolic memory in the liver. Our data provide a useful resource for the study of liver metabolism during fasting.

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“…Moreover, inappropriate feeding behaviour in children with FASD, as well as altered glucose metabolism and insulin tolerance in PAE animals have been reported (Werts et al, 2014; Harper et al 2014). As Rgs3 negatively regulates glucose output via cAMP production in hepatic cells, it may also play a role in altered energy metabolism within the brain when combined with the activation of gastrin and leptin in the PFC (Raab et al, 2005). Furthermore, the activation of interferon- γ in the HPC supports a role for this cytokine in the altered immune system activity and response to challenge in PAE offspring.…”

Section: Discussionmentioning

confidence: 99%

Prenatal Alcohol Exposure Alters Steady‐State and Activated Gene Expression in the Adult Rat Brain

Lussier

Stępień

Neumann

et al. 2015

Alcoholism Clin & Exp Res

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Background Prenatal alcohol exposure (PAE) is associated with alterations in numerous physiological systems, including the stress and immune systems . We have previously shown that PAE increases the course and severity of arthritis in an adjuvant-induced arthritis (AA) model. While the molecular mechanisms underlying these effects are not fully known, changes in neural gene expression are emerging as important factors in the etiology of PAE effects. As the prefrontal cortex (PFC) and hippocampus (HPC) play key roles in neuroimmune function, PAE-induced alterations to their transcriptome may underlie abnormal steady-state functions and responses to immune challenge. The current study examined brains from adult PAE and control females from our recent AA study to determine whether PAE causes long-term alterations in gene expression and whether these mediate the altered severity and course of arthritis in PAE females Methods Adult females from PAE, pair-fed [PF], and ad libitum-fed control [C]) groups were injected with either saline or complete Freund’s adjuvant. Animals were terminated at the peak of inflammation or during resolution (days 16 and 39 post-injection, respectively); cohorts of saline-injected PAE, PF and C females were terminated in parallel. Gene expression was analyzed in the PFC and HPC using whole genome mRNA expression microarrays. Results Significant changes in gene expression in both the PFC and HPC were found in PAE compared to controls in response to ethanol exposure alone (saline-injected females), including genes involved in neurodevelopment, apoptosis, and energy metabolism. Moreover, in response to inflammation (adjuvant-injected females), PAE animals showed unique expression patterns, while failing to exhibit the activation of genes and regulators involved in the immune response observed in control and pair-fed animals. Conclusions These results support the hypothesis that PAE affects neuroimmune function at the level of gene expression, demonstrating long-term effects of PAE on the CNS response under steady-state conditions and following an inflammatory insult.

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Regulation of mouse hepatic genes in response to diet induced obesity, insulin resistance and fasting induced weight reduction

Cited by 17 publications

References 55 publications

Neurogenomic insights into paternal care and its relation to territorial aggression

Neurogenomic insights into paternal care and its relation to territorial aggression

Probing metabolic memory in the hepatic response to fasting

Prenatal Alcohol Exposure Alters Steady‐State and Activated Gene Expression in the Adult Rat Brain

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