Non-alcoholic fatty liver disease (NAFLD) is an important co-morbidity associated with obesity and a precursor to steatohepatitis. However, the contributions of gestational and early life influences on development of NAFLD and NASH remain poorly appreciated. Two independent studies were performed to examine whether maternal over-nutrition via exposure to high fat diet (HFD) leads to exacerbated hepatic responses to post-natal HFD and methionine choline deficient (MCD) diets in the offspring. Offspring of both control diet- and HFD-fed dams were weaned onto control and HFD, creating four groups. When compared to their control diet-fed littermates, offspring of HF-dams weaned onto HFD gained greater body weight; had increased relative liver weight and showed hepatic steatosis and inflammation. Similarly, this group revealed significantly greater immune response and pro-fibrogenic gene expression via RNA-seq. In parallel, 7–8 week old offspring were challenged with either control or MCD diets for 3 weeks. Responses to MCD diets were also exacerbated due to maternal HFD as seen by gene expression of classical pro-fibrogenic genes. Quantitative genome-scale DNA methylation analysis of over 1 million CpGs showed persistent epigenetic changes in key genes in tissue development and metabolism (Fgf21, Ppargc1β) with maternal HFD and in cell adhesion and communication (VWF, Ephb2) in the combination of maternal HFD and offspring MCD diets. Maternal HFD also influenced gut microbiome profiles in offspring leading to a decrease in α-diversity. Linear regression analysis revealed association between serum ALT levels and Coprococcus, Coriobacteriacae, Helicobacterioceae and Allobaculum. Our findings indicate that maternal HFD detrimentally alters epigenetic and gut microbiome pathways to favor development of fatty liver disease and its progressive sequelae.

Adipose tissue (AT) is classified based on its location, physiological and functional characteristics. Although there is a clear demarcation of anatomical and molecular features specific to white (WAT) and brown adipose tissue (BAT), the factors that uniquely differentiate beige AT (BeAT) remain to be fully elaborated. The ubiquitous presence of different types of AT and the inability to differentiate brown and beige adipocytes because of similar appearance present a challenge when classifying them one way or another. Here we will provide an overview of the latest advances in BeAT, BAT, and WAT identification based on transcript markers described in the literature. The review paper will highlight some of the difficulties these markers pose and will offer new perspectives on possible transcript-specific identification of BeAT. We hope that this will advance the understanding of the biology of different ATs. In addition, concrete strategies to distinguish different types of AT may be relevant to track the efficacy and mechanisms around interventions aimed to improve metabolic health and thwart excessive weight gain.

Obesity is a complex, multifactorial disease that has been extensively researched in recent times. Obesity is characterized by excess deposition of adipose tissue in response to surplus energy. Despite the negative connotations of adipose tissue (AT), it serves as a critical endocrine organ. Adipose tissue is a source of several adipokines and cytokines which have been deemed important for both normal metabolic function and disease formation. The discoveries of metabolically active brown AT in adult humans and adipose tissue derived stem cells (ADSC) have been key findings in the past decade with potential therapeutic implications. ADSCs represent an enticing pool of multipotent adult stem cells because of their noncontroversial nature, relative abundance, ease of isolation, and expandability. A decade and a half since the discovery of ADSCs, the scientific community is still working to uncover their therapeutic potential in a wide range of diseases. In this review, we provide an overview of the recent developments in the field of ADSCs and examine their potential use in transplantation and cell‐based therapies for the regeneration of diseased organs and systems. We also hope to provide perspective on how to best utilize this readily available, powerful pool of stem cells in the future.

The gut microflora is a vital component of the gastrointestinal (GI) system that regulates local and systemic immunity, inflammatory response, the digestive system, and overall health. Older people commonly suffer from inadequate nutrition or poor diets, which could potentially alter the gut microbiota. The essential amino acid (AA) tryptophan (TRP) is a vital diet component that plays a critical role in physiological stress responses, neuropsychiatric health, oxidative systems, inflammatory responses, and GI health. The present study investigates the relationship between varied TRP diets, the gut microbiome, and inflammatory responses in an aged mouse model. We fed aged mice either a TRP-deficient (0.1%), TRP-recommended (0.2%), or high-TRP (1.25%) diet for eight weeks and observed changes in the gut bacterial environment and the inflammatory responses via cytokine analysis (IL-1a, IL-6, IL-17A, and IL-27). The mice on the TRP-deficient diets showed changes in their bacterial abundance of Coriobacteriia class, Acetatifactor genus, Lachnospiraceae family, Enterococcus faecalis species, Clostridium sp genus, and Oscillibacter genus. Further, these mice showed significant increases in IL-6, IL-17A, and IL-1a and decreased IL-27 levels. These data suggest a direct association between dietary TRP content, the gut microbiota microenvironment, and inflammatory responses in aged mice models.

The contributions of maternal diet and obesity in shaping offspring microbiome remain unclear. Here we employed a mouse model of maternal diet-induced obesity via high-fat diet feeding (HFD, 45% fat calories) for 12 wk prior to conception on offspring gut microbial ecology. Male and female offspring were provided access to control or HFD from weaning until 17 wk of age. Maternal HFD-associated programming was sexually dimorphic, with male offspring from HFD dams showing hyper-responsive weight gain to postnatal HFD. Likewise, microbiome analysis of offspring cecal contents showed differences in α-diversity, β-diversity and higher Firmicutes in male compared to female mice. Weight gain in offspring was significantly associated with abundance of Lachnospiraceae and Clostridiaceae families and Adlercreutzia, Coprococcus and Lactococcus genera. Sex differences in metagenomic pathways relating to lipid metabolism, bile acid biosynthesis and immune response were also observed. HFD-fed male offspring from HFD dams also showed worse hepatic pathology, increased pro-inflammatory cytokines, altered expression of bile acid regulators (Cyp7a1, Cyp8b1 and Cyp39a1) and serum bile acid concentrations. These findings suggest that maternal HFD alters gut microbiota composition and weight gain of offspring in a sexually dimorphic manner, coincident with fatty liver and a pro-inflammatory state in male offspring.