Thwarting Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) with Common Bean: Dose- and Sex-Dependent Protection against Hepatic Steatosis.

Hepatic steatosis signifies onset of metabolic dysfunction-associated fatty liver disease (MAFLD) caused by disrupted metabolic homeostasis compromising liver function. Regular consumption of common beans reduces the risk of metabolic impairment, but its effective dose, the impact of biological sex, and underlying mechanisms of action are unknown. We fed female and male C57BL6/J mice with obesogenic yet isocaloric diets containing 0%, 17.5%, 35%, and 70% of total dietary protein derived from cooked whole common beans. Liver tissue was collected for histopathology, lipid quantification, and RNA-seq analyses. Beans qualitatively and quantitatively diminished hepatic fat deposition at the 35% dose in female and 70% dose in male mice. Bean-induced differentially expressed genes (DEGs) most significantly mapped to hepatic steatosis and revealed dose-responsive inhibition of de novo lipogenesis markers (Acly, Acaca, Fasn, Elovl6, Scd1, etc.) and triacylglycerol biosynthesis, activation of triacylglycerol degradation, and downregulation of sterol regulatory element-binding transcription factor 1 (SREBF1) signaling. Upregulated fatty acid ß-oxidation was more prominent in females, while suppression of Cd36-mediated fatty acid uptake-in males. Sex-dependent bean effects also involved DEGs patterns downstream of peroxisome proliferator-activated receptor α (PPARα) and MLX-interacting protein-like (MLXIPL). Therefore, biological sex determines amount of common bean in the diet required to prevent hepatic lipid accumulation.

Capillary Western Immunoassay Optimization of Estrogen Related Factors in Human Subcutaneous Adipose Tissue.

Lipedema is a multifaceted chronic fat disorder characterized by the bilateral and disproportionate accumulation of fat predominantly in the lower body regions of females. Research strongly supports that estrogen factors likely contribute to the pathophysiology of this disease. We aim to help demonstrate this link by quantifying estrogen factor differences between women with and without lipedema. For time and lipedema adipose tissue conservation, the Protein Simple WES machine will be utilized in place of traditional western blotting. Here, we are interested in evaluating estrogen related factors, such as, but not limited to, estrogen receptors and enzymes involved in the successive conversions of cholesterol and androgens to estrogens in human subcutaneous adipose. Evaluation of these factors within adipose tissue, however, is novel for this instrument. Thus, we optimized tissue lysis and protein extraction for 11 proteins of interest. Antibodies and their working concentrations were determined based upon specific and distinguishable (signal-to-noise) peaks from electropherogram outputs across different tissue lysate concentrations. We found that overnight acetone precipitation proved to be the best procedure for extracting protein from lipid rich adipose tissue samples. Six of the eleven proteins were found to migrate to their expected molecular weights, however, five did not. For proteins that did not migrate as expected, overexpression lysates and empty vector controls were used to validate detection antibodies. Protein extract from subcutaneous adipose tissue and overexpression lysates were then combined to understand if migration was specifically altered by adipose tissue. From these results, we concluded that the lipid rich nature of adipose tissue in combination with the separation matrix designated for use with the WES were preventing the appropriate migration of some proteins rather than non-specific antibody binding or inappropriate preparation methods.

Relandscaping the Gut Microbiota with a Whole Food: Dose-Response Effects to Common Bean.

Underconsumption of dietary fiber and the milieu of chemicals with which it is associated is a health concern linked to the increasing global burden of chronic diseases. The benefits of fiber are partially attributed to modulation of the gut microbiota, whose composition and function depend on the amount and quality of microbiota-accessible substrates in the diet. However, not all types of fiber are equally accessible to the gut microbiota. Phaseolus vulgaris L., or common bean, is a food type rich in fiber as well as other prebiotics posing a great potential to positively impact diet-microbiota-host interactions. To elucidate the magnitude of bean's effects on the gut microbiota, increasing doses of common bean were administered in macronutrient-matched diet formulations. The microbial communities in the ceca of female and male mice were evaluated via 16S rRNA gene sequencing. As the bean dose increased, the Bacillota:Bacteroidota ratio (formerly referred to as the Firmicutes:Bacteroidetes ratio) was reduced and α-diversity decreased, whereas the community composition was distinctly different between the diet groups according to ß-diversity. These effects were more pronounced in female mice compared to male mice. Compositional analyses identified a dose-responsive bean-induced shift in microbial composition. With an increasing bean dose, Rikenellaceae, Bacteroides, and RF39, which are associated with health benefits, were enhanced. More taxa, however, were suppressed, among which were Allobaculum, Oscillospira, Dorea, and Ruminococcus, which are predominantly associated with chronic disease risk. Investigation of the origins of the dose dependent and biological sex differences in response to common bean consumption may provide insights into bean-gut microbiota-host interactions important to developing food-based precision approaches to chronic disease prevention and control.

Lipedema and the Potential Role of Estrogen in Excessive Adipose Tissue Accumulation.

Lipedema is a painful fat disorder that affects ~11% of the female population. It is characterized by bilateral, disproportionate accumulation of subcutaneous adipose tissue predominantly in the lower body. The onset of lipedema pathophysiology is thought to occur during periods of hormonal fluctuation, such as puberty, pregnancy, or menopause. Although the identification and characterization of lipedema have improved, the underlying disease etiology remains to be elucidated. Estrogen, a key regulator of adipocyte lipid and glucose metabolism, and female-associated body fat distribution are postulated to play a contributory role in the pathophysiology of lipedema. Dysregulation of adipose tissue accumulation via estrogen signaling likely occurs by two mechanisms: (1). altered adipocyte estrogen receptor distribution (ERα/ERß ratio) and subsequent metabolic signaling and/or (2). increased release of adipocyte-produced steroidogenic enzymes leading to increased paracrine estrogen release. These alterations could result in increased activation of peroxisome proliferator-activated receptor γ (PPARγ), free fatty acid entry into adipocytes, glucose uptake, and angiogenesis while decreasing lipolysis, mitochondriogenesis, and mitochondrial function. Together, these metabolic alterations would lead to increased adipogenesis and adipocyte lipid deposition, resulting in increased adipose depot mass. This review summarizes research characterizing estrogen-mediated adipose tissue metabolism and its possible relation to excessive adipose tissue accumulation associated with lipedema.

Examining the Gastrointestinal and Immunomodulatory Effects of the Novel Probiotic Bacillus subtilis DE111.

Probiotics make up a large and growing segment of the commercial market of dietary supplements and are touted as offering a variety of human health benefits. Some of the purported positive impacts of probiotics include, but are not limited to, stabilization of the gut microbiota, prevention of gastrointestinal disorders and modulation of the host immune system. Current research suggests that the immunomodulatory effects of probiotics are strain-specific and vary in mode of action. Here, we examined the immunomodulatory properties of Bacillus subtilis strain DE111 in a healthy human population. In a pilot randomized, double blind, placebo-controlled four-week intervention, we examined peripheral blood mononuclear cells (PBMCs) at basal levels pre- and post-intervention, as well as in response to stimulation with bacterial lipopolysaccharide (LPS). We observed an increase in anti-inflammatory immune cell populations in response to ex vivo LPS stimulation of PBMCs in the DE111 intervention group. Overall perceived gastrointestinal health, microbiota, and circulating and fecal markers of inflammation (Il-6, sIgA) and gut barrier function (plasma zonulin) were largely unaffected by DE111 intervention, although the study may have been underpowered to detect these differences. These pilot data provide information and justification to conduct an appropriately powered clinical study to further examine the immunomodulatory potential of B. subtilis DE111 in human populations.

Comprehensive Evaluation of Metabolites and Minerals in 6 Microgreen Species and the Influence of Maturity.

BACKGROUND: Microgreens are the young leafy greens of many vegetables, herbs, grains, and flowers with potential to promote human health and sustainably diversify the global food system. For successful further integration into the global food system and evaluation of their health impacts, it is critical to elucidate and optimize their nutritional quality. OBJECTIVES: We aimed to comprehensively evaluate the metabolite and mineral contents of 6 microgreen species, and the influence of maturity on their contents. METHODS: Plant species evaluated were from the Brassicaceae (arugula, broccoli, and red cabbage), Amaranthaceae (red beet and red amaranth), and Fabaceae (pea) plant families. Nontargeted metabolomics and ionomics analyses were performed to examine the metabolites and minerals, respectively, in each microgreen species and its mature counterpart. RESULTS: Nontargeted metabolomics analysis detected 3321 compounds, 1263 of which were annotated and included nutrients and bioactive compounds. Ionomics analysis detected and quantified 26 minerals including macrominerals, trace minerals, ultratrace minerals, and other metals. Principal component analysis indicated that microgreens have distinct metabolite and mineral profiles compared with one another and with their mature counterparts. Several compounds were higher (P  < 0.05; fold change ≥2) in microgreens compared with their mature counterparts, whereas some were not different or lower. In many cases, compounds that were higher in microgreens compared with the mature counterpart were also unique to that microgreen species. CONCLUSIONS: These data provide evidence for the nutritional quality of microgreens, and can inform future research and development aimed at characterizing and optimizing microgreen nutritional quality and health impacts.

Microgreens: Consumer sensory perception and acceptance of an emerging functional food crop.

Microgreens are an emerging functional food crop with promise for sustainably diversifying global food systems, facilitating adaptations to urbanization and global climate change, and promoting human health. Previous work suggests microgreens have high nutritional quality, low environmental impacts, and broad consumer acceptance. For better reception into the global food system and increased per capita consumption, research is needed to elucidate consumer acceptance of various microgreens species, including factors contributing to their acceptance or lack thereof. Using a consumer panel (n = 99), this study evaluated consumer sensory perception and acceptability of six microgreens species (arugula, broccoli, bull's blood beet, red cabbage, red garnet amaranth, and tendril pea), and potential drivers and barriers to consumer acceptance. All microgreens species received high mean liking scores for acceptability by consumers (means ranged from highly acceptable to slightly acceptable), with more distinct differences across microgreens species for flavor and overall acceptability, which appeared to be driven by specific sensory properties. Data from principal component analysis demonstrated that high acceptability scores were associated with higher intent to purchase microgreens and negatively associated with food neophobia. Participants indicated that factors such as knowledge and familiarity of microgreens, cost, access/availability, freshness/shelf life, among other factors, influence their intention to purchase microgreens. These findings suggest that further integration of microgreens into the global food system will be met with high consumer acceptability, but needs to be aligned with enhanced consumer education regarding microgreens, as well as considerations of cost, availability/access, and freshness/shelf life. PRACTICAL APPLICATION: Researchers investigated consumer sensory perception and acceptability of six microgreens species (arugula, broccoli, bull's blood beet, red cabbage, red garnet amaranth, and tendril pea), and potential drivers and barriers to consumer acceptance. All microgreens tested had high consumer acceptability, but certain factors such as sensory perception and food neophobia impacted their acceptability. Additionally, participants indicated that factors such as knowledge, access and availability, cost, freshness, and shelf life may impact the purchasing of microgreens and thus are important factors to consider for further integration of this emerging functional food crop into the global food system.

High-fat diet induced central adiposity (visceral fat) is associated with increased fibrosis and decreased immune cellularity of the mesenteric lymph node in mice.

PURPOSE: Accumulation of visceral, but not subcutaneous, adipose tissue is highly associated with metabolic disease. Inflammation inciting from adipose tissue is commonly associated with metabolic disease risk and comorbidities. However, constituents of the immune system, lymph nodes, embedded within these adipose depots remain under-investigated. We hypothesize that, lymph nodes are inherently distinct and differentially respond to diet-induced obesity much like the adipose depots they reside in. METHODS: Adipose tissue and lymph nodes were collected from the visceral and inguinal depots of male mice fed 13 weeks of standard CHOW or high fat diet (HFD). Immune cells were isolated from tissues, counted and characterized by flow cytometry or plated for proliferative capacity following Concanavalin A stimulation. Lymph node size and fibrosis area were also characterized. RESULTS: In HFD fed mice visceral adipose tissue accumulation was associated with significant enlargement of the lymph node encased within. The subcutaneous lymph node did not change. Compared with mice fed CHOW for 13 weeks, mice fed HFD had a decline in immune cell populations and immune cell proliferative ability, as well as, exacerbated fibrosis accumulation, within the visceral, but not subcutaneous, lymph node. CONCLUSIONS: Obesity-induced chronic low-grade inflammation is associated with impaired immunity and increased susceptibility to disease. Excessive visceral adiposity and associated inflammation driven by diet likely leads to obesity-induced immune suppression by way of lymph node/lymphatic system pathophysiology.

Glucocorticoids regulate adipose tissue protein concentration in a depot- and sex-specific manner.

Preclinical and clinical findings indicate that glucocorticoids (GC) induce lipid accumulation in visceral depots, while inhibiting lipid stores from subcutaneous depots. Whereas some suggest that this is due to adipose depot specific concentration of glucocorticoid receptors (GR) or 11beta-hydroxysteroid dehydrogenase 1 (11ß-HSD1), others demonstrate these events emerge from increases in interleukin-1 beta (IL-1ß) from macrophages within distinct depots. Regardless of the mechanisms, most of these studies occur in males and thus lack evaluation of sex differences. Here, we examined the impact of 2-week corticosterone (CORT) (3 mg/kg/day) or saline treatment on GR, 11ß-HSD1 and IL-1ß protein concentration in intra-abdominal (epididymal/parametrial, and visceral) and subcutaneous (inguinal) depots in male and female Sprague Dawley rats. The objective was to examine if factors that regulate GC-induced adipose depot metabolism and distribution, differ between males and females. CORT inhibited, but did not decrease, body weight gain in both sexes. 11ß-HSD1 was similar between the sexes in all adipose depots. CORT increased IL-1ß in both sexes only in gonadal adipose tissue. Overall, males had greater GR protein concentration in all adipose depots, whereas females had more IL-1ß in intra-abdominal adipose depots. Given the male-biased increase in intra-abdominal GR protein concentration, the data suggest that males may be more prone to CORT-induced increases in visceral obesity, which may have implications for increased risk for metabolic diseases. Overall, the data suggest that the effects of GC signaling in adipose tissue are multifaceted, dependent on sex, and the inherent adipocyte characteristics.Lay summaryResearch supports that glucocorticoids (GC) induce visceral adipose tissue accumulation, however few studies have examined if these GC-mediated outcomes are similar between males and females. This study investigates if female rats differentially respond to corticosterone treatment. Results indicate that male rats may have an increased susceptibility to CORT-induced accumulation of visceral adipose tissue compared with females, which may have implication for sex-specific risk for metabolic diseases.

White Kidney Bean (Phaseolus Vulgaris L.) Consumption Reduces Fat Accumulation in a Polygenic Mouse Model of Obesity.

Clinical studies indicate that eating common bean, Phaseolus vulgaris L., plays a role in body weight regulation but mechanisms have yet to be elucidated. Here, we investigated the anti-obesogenic activity of white kidney bean in a mouse model of dietary-induced obesity. Bean consumption reduced the accumulation of adipose tissue in male and female C57BL6 mice. The anti-obesogenic effect of white kidney bean was not due to alterations in energy intake, energy excreted in the feces, or feed efficiency ratio. While bean consumption increased the mass of the intestine, no marked differences were consistently observed in crypt height, mucin content of goblet cells, proliferation index or zone of proliferation. However, significantly higher concentrations of total bacteria and of Akkermansia muciniphila were detected in cecal content of bean-fed mice, and the ratio of Firmicutes to Bacteroidetes was reduced. Bile acid content was higher in the ileum of bean-fed mice, but transcript levels of farnesoid X receptor were not significantly affected. Whether changes in bile-acid-mediated cell signaling play a role in bean-related differences in fat accumulation and/or overall metabolic health requires further investigation.

Obesity-induced immune dysfunction and immunosuppression: TEM observation of visceral and subcutaneous lymph node microarchitecture and immune cell interactions.

Background Inflammation, induced by excessive adiposity, links obesity to disease risk yet little attention has been devoted to the lymphoid tissues embedded within adipose tissue depots. Lymph nodes are the primary site for the development of protective immunity, hence any disease process that affects these tissues will also directly impact immunity. Here we examined how obesity alters secondary lymphatic tissue structure and encapsulated immune cells. Materials and methods Four-month-old C57BL/6 male mice were fed standard rodent chow or a Western high fat diet (HFD) for 6 months. Center regions of visceral and subcutaneous lymph nodes (SQLNS) were observed via transmission electron microscopy (TEM). Results Compared with chow, HFD-induced obesity deleteriously modified the structural microarchitecture and immune cell morphology of visceral and SQLNs. In HFD mice, fibroblastic reticular cells (FRCs) were dysregulated while laying among excessive amounts of disorganized collagen (C). In addition HFD lymph nodes contained a disproportionate amount of cellular debris from damaged or dead cells, increased sinus spacing and decreased immune cell interactions. Specifically, dendritic cells (DCs) that are necessary for adaptive immune response where embedded among extracellular debris with decreased pseudopodia. Similarly, the extraneous fibrous extracellular matrix (ECM) in HFD mice limited contact between lymphocytes (LCs) causing their microvilli extensions to decrease. Discussion Overall, excessive C production within lymph nodes, driven by diet-induced obesity, creates a physical barrier that impedes proper lymph flow and cellular communication. Obesity-induced disorganization of the immune cell guidance network interrupts immune cell adhesion and consequently inhibits travel within cortex regions needed for cell interactions, survival and proliferation.

Summary of the 2018 Alcohol and Immunology Research Interest Group (AIRIG) meeting.

On January 26, 2018, the 23rd annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at the University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado. The meeting consisted of plenary sessions with oral presentations and a poster presentation session. There were four plenary sessions that covered a wide range of topics relating to alcohol use: Alcohol and Liver Disease; Alcohol, Inflammation and Immune Response; Alcohol and Organ Injury; Heath Consequences and Alcohol Drinking. The meeting provided a forum for the presentation and discussion of novel research findings regarding alcohol use and immunology.

Obesity associated disease risk: the role of inherent differences and location of adipose depots.

Obesity and associated metabolic co-morbidities are a worldwide public health problem. Negative health outcomes associated with obesity, however, do not arise from excessive adiposity alone. Rather, deleterious outcomes of adipose tissue accumulation are a result of how adipocytes are distributed to individual regions in the body. Due to our increased understanding of the dynamic relationship that exists between specific adipose depots and disease risk, an accurate characterization of total body adiposity as well as location is required to properly evaluate a population's disease risk. Specifically, distinctive tissue depots within the body include the lower body, upper body and abdominal (deep and superficial) subcutaneous regions, as well as visceral (mesenteric and omental) regions. Upper body and visceral adipose tissues are highly associated with metabolic dysfunction and chronic disease development, whereas lower body gluteofemoral subcutaneous adipose tissue imparts protection against diet-induced metabolic derangement. Each adipose depot functions distinctly as an endocrine organ hence it has a different level of impact on health outcomes. Effluent from adipose tissue can modulate the functions of other tissues, whilst receiving differential communication from the rest of the body via central nervous system innervation, metabolites and other signaling molecules. More so, adipose depots contain a diverse reservoir of tissue-resident immune cells that play an integral part in both maintaining tissue homeostasis, as well as propagating metabolically-induced inflammation. Overall, the conceptualization of obesity and associated risks needs updating to reflect the complexities of obesity. We review adipose tissue characteristics that are linked to deleterious or beneficial adipose tissue distributions.

Adipose tissue extrinsic factor: Obesity-induced inflammation and the role of the visceral lymph node.

Obesity-related adverse health consequences occur predominately in individuals with upper body fat distribution commonly associated with increased central adiposity. Visceral adipose tissue accumulation is described to be the greatest driver of obesity-induced inflammation, however evidence also supports that the intestines fundamentally contribute to the development of obesity-induced metabolic disease. The visceral adipose depot shares the same vasculature and lymph drainage as the small intestine. We hypothesize that the visceral lymph node, which drains adipose tissue and the gastrointestinal tract, is central to the exacerbation of systemic pro-inflammation. Male C57BL/6 mice were fed CHOW or high fat diet (HFD) for 7 weeks. At termination the mesenteric depot, visceral lymph node and ileum, jejunum and Peyer's patches were collected. Cytokine concentration was determined in adipose tissue whereas immune cell populations where investigated in the visceral lymph node and intestinal segments by flow cytometry. Visceral adipose tissue and the gastrointestinal tract mutually influence immune cells enclosed within the visceral lymph node. HFD increased visceral lymph node immune cell number. This likely resulted from 1.) an increase in immune cells migration from the small intestines likely from activated dendritic cells that travel to the lymph node and 2.) cytokine effluent from visceral adipose tissue that promoted expansion, survival and retention of pro-inflammatory immune cells. Overall, the visceral lymph node, the immune nexus of visceral adipose tissue and the small intestines, likely plays a fundamental role in exacerbation of systemic pro-inflammation by HFD-induced obesity. The research of Tim Bartness greatly enhanced the understanding of adipose tissue regulation. Studies from his laboratory significantly contributed to our awareness of extrinsic factors that influence body fatness levels. Specifically, the work he produced eloquently demonstrated that adipose tissue was more complex than an insulating storage center; it was connected to our brains via the sympathetic and sensory nervous system. Mapping studies demonstrated that adipose tissue both receives and sends information to the brain. Further, his lab demonstrated that nervous system connections contributed to lipolysis, thermogenesis and adipocyte proliferation and growth. The work of Tim Bartness will continue to influence adipose tissue research. As such, Tim Bartness directly inspired the following research. Adipose tissue extrinsic factors are not limited to the peripheral nervous system. The lymphatic system is an additional extrinsic factor that cross talks with adipose tissue, however its role in this context is under emphasized. Here we begin to elucidate how the lymphatic system may contribute to the comorbidities associated with visceral adipose tissue accumulation.

Subcutaneous inguinal white adipose tissue is responsive to, but dispensable for, the metabolic health benefits of exercise.

Exercise training has robust effects on subcutaneous inguinal white adipose tissue (iWAT), characterized by a shift to a brown adipose tissue (BAT)-like phenotype. Consistent with this, transplantation of exercise-trained iWAT into sedentary rodents activates thermogenesis and improves glucose homeostasis, suggesting that iWAT metabolism may contribute to the beneficial effects of exercise. However, it is yet to be determined if adaptations in iWAT are necessary for the beneficial systemic effects of exercise. To test this, male C57BL/6 mice were provided access to voluntary wheel running (VWR) or remained as a cage control (SED) for 11 nights after iWAT removal via lipectomy (LIPX) or SHAM surgery. We found that SHAM and LIPX mice with access to VWR ran similar distances and had comparable reductions in body mass, increased food intake, and increased respiratory exchange ratio (RER). Further, VWR improved indexes of glucose homeostasis and insulin tolerance in both SHAM and LIPX mice. The lack of effect of LIPX in the response to VWR was not explained by compensatory increases in markers of mitochondrial biogenesis and thermogenesis in skeletal muscle, epididymal white adipose tissue, or interscapular brown adipose tissue. Together, these data demonstrate that mice with and without iWAT have comparable adaptations to VWR, suggesting that iWAT may be dispensable for the metabolic health benefits of exercise.

Beiging of white adipose tissue as a therapeutic strategy for weight loss in humans.

An imbalance between energy intake and expenditure leads to obesity. Adiposity associated with obesity progressively causes inflammation, type 2 diabetes, hypertension, hyperlipidemia and cardiovascular disease. Excessive dietary intake of fat results in its accumulation and storage in the white adipose tissue (WAT), whereas energy expenditure by fat utilization and oxidation predominately occurs in the brown adipose tissue (BAT). Recently, the presence of a third type of fat, referred to as beige or brite (brown in white), has been recognized in certain kinds of WAT depots. It has been suggested that WAT can undergo the process of browning in response to stimuli that induce and enhance the expression of thermogenes characteristic of those typically associated with brown fat. The resultant beige or brite cells enhance energy expenditure by reducing lipids stored within adipose tissue. This has created significant excitement towards the development of a promising strategy to induce browning/beiging in WAT to combat the growing epidemic of obesity. This review systematically describes differential locations and functions of WAT and BAT, mechanisms of beiging of WAT and a concise analysis of drug molecules and natural products that activate the browning phenomenon in vitro and in vivo. This review also discusses potential approaches for targeting WAT with compounds for site-specific beiging induction. Overall, there are numerous mechanisms that govern browning of WAT. There are a variety of newly identified targets whereby potential molecules can promote beiging of WAT and thereby combat obesity.

Susceptibility or resilience? Prenatal stress predisposes male rats to social subordination, but facilitates adaptation to subordinate status.

Mood disorders such as major depressive disorder (MDD) affect a significant proportion of the population. Although progress has been made in the development of therapeutics, a large number of individuals do not attain full remission of symptoms and adverse side effects affect treatment compliance for some. In order to develop new therapies, there is a push for new models that better reflect the multiple risk factors that likely contribute to the development of depressive illness. We hypothesized that early life stress would exacerbate the depressive-like phenotype that we have previously observed in socially subordinate (SUB) adult male rats in the visible burrow system (VBS), a semi-natural, ethologically relevant environment in which males in a colony form a dominance hierarchy. Dams were exposed to chronic variable stress (CVS) during the last week of gestation, resulting in a robust and non-habituating glucocorticoid response that did not alter maternal food intake, body weight or litter size and weight. As adults, one prenatal CVS (PCVS) and one non-stressed (NS) male were housed in the VBS with adult females. Although there were no overt differences between PCVS and NS male offspring prior to VBS housing, a greater percentage of PCVS males became SUB. However, the depressive-like phenotype of SUB males was not exacerbated in PCVS males; rather, they appeared to better cope with SUB status than NS SUB males. They had lower basal plasma corticosterone than NS SUB males at the end of VBS housing. In situ hybridization for CRH in the PVN and CeA did not reveal any prenatal treatment or status effects, while NPY expression was higher within the MeA of dominant and subordinate males exposed to the VBS in comparison with controls, but with no effect of prenatal treatment. These data suggest that prenatal chronic variable stress may confer resilience to offspring when exposed to social stress in adulthood.

So as we worry we weigh: Visible burrow system stress and visceral adiposity.

The visible borrow system (VBS) simulates a natural rodent habitat that supports genuine stress provoking social interactions. This model allows investigation of behavioral, neural and endocrine alterations caused by chronic stress. The Sakai lab further used this model to investigate metabolic outcomes of stress in relation to dominance hierarchies formed within the VBS. Communal social conflict occurs among all VBS rats, but only the SUB rats succumb to the redistribution of lipids in the visceral cavity and consequent metabolic dysregulation, such as hyper-insulinemia. These increases in visceral adipose tissue occur after two cycles of VBS stress and recovery bouts and are associated with decreases in subcutaneous adipose tissue. Traditionally, distribution shift in lipid deposition is predominately thought to occur by characteristics specific to the visceral depot, but evidence supports that decreased subcutaneous adipose tissue deposition may be linked to enhanced visceral adipose expansion. This review will discuss VBS stress and redirection of adipose tissue in SUB rats. There will be specific focus on the enhanced adipogenic capacity of visceral adipose tissue as driven by glucocorticoid receptor density, 11-hydroxysteroid dehydrogenase type 1 (11-HSD1) and lipoprotein lipase (LPL). Additionally, the proposed contribution of decreased subcutaneous adipose expansion via stress-induced inhibition of lipid uptake, storage and cellularity will be discussed. Overall, this review will summarize how stress-induced visceral obesity may result from a combination of maladaptive responses within the visceral and subcutaneous depot.

Fuzhuan tea reverses arterial stiffening after modest weight gain in mice.

OBJECTIVES: The aim of this study was to examine the effects of a Western diet (WD) and supplementation with Fuzhuan tea on large artery stiffness, as determined by aortic pulse wave velocity (aPWV). METHODS: Mice were subjected to a standard diet (SD; n = 12) or WD (n = 10) for 7 mo, and were then separated to receive nonsupplemented drinking water (SD-W and WD-W) or water supplemented with Fuzhuan tea (SD-T and WD-T) (200 mg/kg daily); mice were then maintained on their respective diets for an additional 2 mo. RESULTS: After the initial 7-mo feeding period, WD elicited a modest and significantly greater increase in body weight than did SD (39.6 ± 0.71 versus 34.5 ± 1.16 g; P < 0.01). PWV was significantly elevated in WD but not in SD (459.3 ± 4.8 versus 422.4 ± 6.4 cm/s; P < 0.001). Following an additional 2 mo, PWV continued to increase in WD-W, but returned to control levels in WD-T (WD-W: 519.8 ± 12.8; WD-T: 426.5 ± 18.6; SD-W: 429.7 ± 8.6; SD-T: 429.1 ± 6.1 cm/s; P < 0.001, WD-W versus all groups). The increase in PWV in WD-W was accompanied by an increase in aortic collagen (WD-W: 38.8 ± 4.6 versus SD-W: 17.5 ± 5.1 percent cross-sectional area; P < 0.05). CONCLUSION: The results of the present study suggest that the increase in arterial stiffness after modest, diet-induced weight gain can be reversed by supplementation with Fuzhuan tea.

Adipose tissue: an endocrine organ playing a role in metabolic regulation.

Adipose tissue is a complex endocrine organ with an intricate role in whole body homeostasis. Beyond storing energy, adipose tissue is fundamental in numerous processes including, but not limited to, metabolism, food intake and immune cell function. Adipokines and cytokines are the signaling factors from adipose tissue. These factors play a role in maintaining health, but are also candidates for pathologies associated with obesity. Indeed excessive adiposity causes dysregulation of these factors which negatively affect health and contribute to numerous obesity-induced co-morbidities. In particular, adipokines are fundamental in regulation of glucose homeostasis and insulin signaling, thus aberrant production of these adipose derived hormones correlates with the development and progression of type 2 diabetes. Therefore, elucidation of adipose regulation is crucial for understanding the pathophysiological basis of obesity and metabolic diseases such as type 2 diabetes. In the present review, we summarize current data on the relation between adipokines and adipose depot derived cytokines in the maintenance of glucose homeostasis. Specifically, physiological and molecular functions of several adipokines are defined with particular focus on interactions within the insulin-signaling pathway and subsequent regulation of glucose uptake in both standard and obesity-induced dysregulated conditions. This same relation will be discussed for cytokines and inflammation as well.