Biology subjects

Shu, L.

Publications and source records attributed to Shu, L..

3 recordsLinked to original sources

bioRxiv2018

Differential Metabolic and Multi-tissue Transcriptomic Responses to Fructose Consumption among Genetically Diverse Mice

High fructose intake is a major risk for metabolic syndrome; however, its effects seem to vary across individuals. To determine main factors involved in the inter-individual responses to fructose, we fed inbred mouse strains C57BL/6J (B6), DBA/2J (DBA) and FVB/NJ (FVB) with fructose. DBA mice showed the highest susceptibility to gain adiposity and glucose intolerance. Elevated insulin was found in DBA and FVB mice, and cholesterol levels were uniquely elevated in B6 mice. The transcriptional profiles of liver, hypothalamus, and adipose tissues showed strain- and tissue-specific pathways altered by fructose, such as fatty acid and cholesterol pathways for B6 and PPAR signaling for DBA in liver, and oxidative phosphorylation for B6 and protein processing for DBA in hypothalamus. Using network modeling, we predicted potential strain-specific key regulators of fructose response such as Fgf21 (DBA) and Lss (B6) in liver, and validated strain-biased responses as well as the regulatory actions of Fgf21 and Lss in primary hepatocytes. Our findings support that fructose perturbs individualized tissue networks and pathways and associates with distinct features of metabolic dysfunctions across genetically diverse mice. Our results elucidate the molecular pathways and gene regulatory mechanisms underlying inter-individual variability in response to high fructose diet.

systems biology↗

bioRxiv2018

A complex symbiosis involving within species variation in the response of Dictyostelium amoebae to Burkholderia bacteria

Recent symbioses, particularly facultative ones, are well suited for unravelling the evolutionary give and take between partners. Here we look at variation in wild-collected samples of the social amoeba Dictyostelium discoideum and their relationships with bacterial symbionts, Burkholderia hayleyella and Burkholderia agricolaris. Only about a third of field-collected amoebae carry a symbiont. We cured and cross-infected D. discoideum hosts with different symbiont association histories and then compared the responses of the amoebae to each symbiont type. Before curing, field-collected clones did not vary significantly in overall fitness, but infected hosts produced morphologically different multicellular structures. After curing and re-infecting, host fitness declined overall. However, natural B. hayleyella hosts suffered fewer fitness costs when re-infected with B. hayleyella, indicating that they have evolved mechanisms to tolerate their naturally acquired symbiont. Exploring relationships between endosymbionts and hosts that vary within species may also reveal much about disease dynamics.

microbiology↗

bioRxiv2018

Prenatal Bisphenol A Exposure in Mice Induces Multi-tissue Multi-omics Disruptions Linking to Cardiometabolic Disorders

The health impacts of endocrine disrupting chemicals (EDCs) remain debated and their tissue and molecular targets are poorly understood. Here we leveraged systems biology approaches to assess the target tissues, molecular pathways, and gene regulatory networks associated with prenatal exposure to the model EDC Bisphenol A (BPA). Prenatal BPA exposure led to scores of transcriptomic and methylomic alterations in the adipose, hypothalamus, and liver tissues in mouse offspring, with cross-tissue perturbations in lipid metabolism as well as tissue-specific alterations in histone subunits, glucose metabolism and extracellular matrix. Network modeling prioritized main molecular targets of BPA, including Pparg, Hnf4a, Esr1, and Fasn. Lastly, integrative analyses identified the association of BPA molecular signatures with cardiometabolic phenotypes in mouse and human. Our multi-tissue, multi-omics investigation provides strong evidence that BPA perturbs diverse molecular networks in central and peripheral tissues, and offers insights into the molecular targets that link BPA to human cardiometabolic disorders.\n\nAuthor summaryThe inability to pinpoint the mechanistic underpinnings of environmentally-induced diseases likely stems from the pleiotropic effects of chemicals such as BPA on diverse tissues and molecular space (transcriptome, epigenome, etc.). This makes it challenging to fully dissect their health impact and merits a call for modern big data approaches to examine environmental factors. Our data-driven study is the first unbiased, multi-tissue multiomic systems biology investigation of the molecular circuitry and mechanisms underlying offspring response to prenatal BPA exposure. Importantly, the incorporation of network-based modeling allows us to capture novel players in the regulation of BPA activities in vivo, and the integration with human disease association datasets helps bridge the molecular pathways affected by BPA with diverse human diseases. In doing so, our study provides compelling molecular evidence that developmental BPA exposure significantly perturbs metabolic and endocrine systems in the offspring, and supports BPA as one of the environmental factors involved in the developmental origins of health and disease (DOHaD).

systems biology↗