ERRγ Preserves Brown Fat Innate Thermogenic Activity

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Is Dietary Fat Intake Related to Liking or Household Availability of High‐ and Low‐Fat Foods?

Objectives : Despite the increasing availability of low‐ and reduced‐fat foods, Americans continue to consume more fat than recommended, which may be a contributing factor to the obesity epidemic. This investigation examined relationships between liking and household availability of high‐ and low‐fat foods and their association with dietary fat intake. Research Methods and Procedures : A food frequency questionnaire assessed percent calories from fat consumed over the past year in 85 men and 80 women. Participants reported their degree of liking 22 “high‐fat foods” (>45% calories from fat) and 22 “low‐fat foods” (<18% calories from fat), and the number and percentage (number of high‐ or low‐fat foods/total number of foods × 100) of these high‐ and low‐fat foods in their homes. Results : Hierarchical regression analyses examined the ability of liking and household availability of low‐ and high‐fat foods to predict percent dietary fat intake. After controlling for age, sex, and BMI, liking ratings for high‐ and low‐fat foods and the interaction of liking for low‐fat foods by the percentage of low‐fat foods in the household were significant predictors of percent dietary fat consumed. Greater liking of high‐fat foods and lower liking of low‐fat foods, both alone and combined with a lower percentage of low‐fat foods in the home, were predictive of higher dietary fat intake. Discussion : Interventions designed to reduce dietary fat intake should target both decreasing liking for high‐fat foods and increasing liking for low‐fat foods, along with increasing the proportion of low‐fat foods in the household.     

Alzheimer’s Disease and Cholesterol: The Fat Connection

Since the discovery of the significance of the cholesterol-carrying apolipoprotein E and cholesterolaemia as major risk factors for Alzheimer's Disease (AD) there has been a mounting interest in the role of this lipid as a possible pathogenic agent. In this review we analyse the current evidence linking cholesterol metabolism and regulation in the CNS with the known mechanisms underlying the development of Alzheimer's Disease. Cholesterol is known to affect amyloid-beta generation and toxicity, although it must be considered that the results studies using the statin class of drugs to lower plasma cholesterol may be affected by other effects associated with these drugs. Finally, we report some of our results pointing at the interplay between neurons and astrocytes and NADPH oxidase activation as a new candidate mechanism linking cholesterol and AD pathology.     

Are Normal‐Weight Americans Over‐Fat?

Data from National Health and Nutrition Examination Surveys (NHANES) 1999-2004 have recently shown the percent body fat of American adults. Average American men and women have ~28 and 40% body fat. When categorized by BMI and age, the data also show high percent body fat values, particularly in lower BMI categories. These data should make one reflect on the health status of Americans in all BMI categories and the use of these data for public health recommendations.     

Differences in Visceral Fat and Fat Bacterial Colonization between Ulcerative Colitis and Crohn’s Disease. An In Vivo and In Vitro Study

Crohn’s disease (CD) is notably characterized by the expansion of visceral fat with small adipocytes expressing a high proportion of anti-inflammatory genes. Conversely, visceral fat depots in ulcerative colitis (UC) patients have never been characterized. Our study aims were a) to compare adipocyte morphology and gene expression profile and bacterial translocation in omental (OM) and mesenteric (MES) adipose tissue of patients with UC and CD, and b) to investigate the effect of bacterial infection on adipocyte proliferation in vitro. Specimens of OM and MES were collected from 11 UC and 11 CD patients, processed and examined by light microscopy. Gene expression profiles were evaluated in adipocytes isolated from visceral adipose tissue using microarray and RTqPCR validations. Bacteria within adipose tissue were immuno-detected by confocal scanning laser microscopy. Adipocytes were incubated with Enterococcus faecalis and cells counted after 24h. Morphology and molecular profile of OM and MES revealed that UC adipose tissue is less inflamed than CD adipose tissue. Genes linked to inflammation, bacterial response, chemotaxis and angiogenesis were down-regulated in adipocytes from UC compared to CD, whereas genes related to metallothioneins, apoptosis pathways and growth factor binding were up-regulated. A dense perinuclear positivity for Enterococcus faecalis was detected in visceral adipocytes from CD, whereas positivity was weak in UC. In vitro bacterial infection was associated with a five-fold increase in the proliferation rate of OM preadipocytes. Compared to UC, visceral adipose tissue from CD is more inflamed and more colonized by intestinal bacteria, which increase adipocyte proliferation. The influence of bacteria stored within adipocytes on the clinical course of IBD warrants further investigations.     

Taranabant Cuts the Fat: New Hope for Cannabinoid-Based Obesity Therapies?

Endocannabinoid/cannabinoid receptor signaling acts centrally and peripherally to govern appetite and energy balance. While system stimulation promotes eating and energy storage, receptor blockade can reduce food intake and facilitate weight loss. In this issue of Cell Metabolism, Addy et al. (2008) test the therapeutic antiobesity potential of taranabant, a cannabinoid 1 receptor inverse agonist.     

SIRT4 Represses Peroxisome Proliferator-Activated Receptor α Activity To Suppress Hepatic Fat Oxidation

Sirtuins are a family of protein deacetylases, deacylases, and ADP-ribosyltransferases that regulate life span, control the onset of numerous age-associated diseases, and mediate metabolic homeostasis. We have uncovered a novel role for the mitochondrial sirtuin SIRT4 in the regulation of hepatic lipid metabolism during changes in nutrient availability. We show that SIRT4 levels decrease in the liver during fasting and that SIRT4 null mice display increased expression of hepatic peroxisome proliferator-activated receptor α (PPARα) target genes associated with fatty acid catabolism. Accordingly, primary hepatocytes from SIRT4 knockout (KO) mice exhibit higher rates of fatty acid oxidation than wild-type hepatocytes, and SIRT4 overexpression decreases fatty acid oxidation rates. The enhanced fatty acid oxidation observed in SIRT4 KO hepatocytes requires functional SIRT1, demonstrating a clear cross talk between mitochondrial and nuclear sirtuins. Thus, SIRT4 is a new component of mitochondrial signaling in the liver and functions as an important regulator of lipid metabolism.     

Myocardial Ischemic Subject’s Thymus Fat: A Novel Source of Multipotent Stromal Cells

Objective

Adipose Tissue Stromal Cells (ASCs) have important clinical applications in the regenerative medicine, cell replacement and gene therapies. Subcutaneous Adipose Tissue (SAT) is the most common source of these cells. The adult human thymus degenerates into adipose tissue (TAT). However, it has never been studied before as a source of stem cells.

Material and Methods

We performed a comparative characterization of TAT-ASCs and SAT-ASCs from myocardial ischemic subjects (n = 32) according to the age of the subjects.

Results

TAT-ASCs and SAT-ASCs showed similar features regarding their adherence, morphology and in their capacity to form CFU-F. Moreover, they have the capacity to differentiate into osteocyte and adipocyte lineages; and they present a surface marker profile corresponding with stem cells derived from AT; CD73⁺CD90⁺CD105⁺CD14^-CD19^-CD45^-HLA-DR. Interestingly, and in opposition to SAT-ASCs, TAT-ASCs have CD14⁺CD34⁺CD133⁺CD45^- cells. Moreover, TAT-ASCs from elderly subjects showed higher adipogenic and osteogenic capacities compared to middle aged subjects, indicating that, rather than impairing; aging seems to increase adipogenic and osteogenic capacities of TAT-ASCs.

Conclusions

This study describes the human TAT as a source of mesenchymal stem cells, which may have an enormous potential for regenerative medicine.     

High Fat Diet Accelerates Pathogenesis of Murine Crohn’s Disease-Like Ileitis Independently of Obesity

Background

Obesity has been associated with a more severe disease course in inflammatory bowel disease (IBD) and epidemiological data identified dietary fats but not obesity as risk factors for the development of IBD. Crohn’s disease is one of the two major IBD phenotypes and mostly affects the terminal ileum. Despite recent observations that high fat diets (HFD) impair intestinal barrier functions and drive pathobiont selection relevant for chronic inflammation in the colon, mechanisms of high fat diets in the pathogenesis of Crohn’s disease are not known. The aim of this study was to characterize the effect of HFD on the development of chronic ileal inflammation in a murine model of Crohn’s disease-like ileitis.

Methods

TNF^ΔARE/WT mice and wildtype C57BL/6 littermates were fed a HFD compared to control diet for different durations. Intestinal pathology and metabolic parameters (glucose tolerance, mesenteric tissue characteristics) were assessed. Intestinal barrier integrity was characterized at different levels including polyethylene glycol (PEG) translocation, endotoxin in portal vein plasma and cellular markers of barrier function. Inflammatory activation of epithelial cells as well as immune cell infiltration into ileal tissue were determined and related to luminal factors.

Results

HFD aggravated ileal inflammation but did not induce significant overweight or typical metabolic disorders in TNF^ΔARE/WT. Expression of the tight junction protein Occludin was markedly reduced in the ileal epithelium of HFD mice independently of inflammation, and translocation of endotoxin was increased. Epithelial cells showed enhanced expression of inflammation-related activation markers, along with enhanced luminal factors-driven recruitment of dendritic cells and Th17-biased lymphocyte infiltration into the lamina propria.

Conclusions

HFD feeding, independently of obesity, accelerated disease onset of small intestinal inflammation in Crohn’s disease-relevant mouse model through mechanisms that involve increased intestinal permeability and altered luminal factors, leading to enhanced dendritic cell recruitment and promoted Th17 immune responses.     

High Fat,Low Carbohydrate Diet Limit Fear and Aggression in G?ttingen Minipigs

High fat, low carbohydrate diets have become popular, as short-term studies show that such diets are effective for reducing body weight, and lowering the risk of diabetes and cardiovascular disease. There is growing evidence from both humans and other animals that diet affects behaviour and intake of fat has been linked, positively and negatively, with traits such as exploration, social interaction, anxiety and fear. Animal models with high translational value can help provide relevant and important information in elucidating potential effects of high fat, low carbohydrate diets on human behaviour. Twenty four young, male Göttingen minipigs were fed either a high fat/cholesterol, low carbohydrate diet or a low fat, high carbohydrate/sucrose diet in contrast to a standard low fat, high carbohydrate minipig diet. Spontaneous behaviour was observed through video recordings of home pens and test-related behaviours were recorded during tests involving animal-human contact and reaction towards a novel object. We showed that the minipigs fed a high fat/cholesterol, low carbohydrate diet were less aggressive, showed more non-agonistic social contact and had fewer and less severe skin lesions and were less fearful of a novel object than minipigs fed low fat, high carbohydrate diets. These results found in a porcine model could have important implications for general health and wellbeing of humans and show the potential for using dietary manipulations to reduce aggression in human society.