Prevention of high-fat diet-induced adipose tissue remodeling in obese diabetic mice by n-3 polyunsaturated fatty acids

Huber, J.F.K.; Löffler, Michael; Bilban, Martin; Reimers, Mark; Kadl, Alexandra; Todoric, Jelena; Zeyda, Maximilian; Geyeregger, René; Schreiner, Matthias; Weichhart, Thomas; Leitinger, Norbert; Waldhäusl, W.; Stulnig, Thomas M.

doi:10.1038/sj.ijo.0803511

Cited by 129 publications

(110 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previous studies have shown that COL6 is abundantly expressed by adipocytes (42), and obese mice have increased COL6 expression in the extracellular matrix (43). We found that overweight/obese subjects with low AT pO 2 have greater expression of COL6, and COL6 expression increased with increased body fat and fat-cell size.…”

Section: Discussionsupporting

confidence: 58%

Reduced Adipose Tissue Oxygenation in Human Obesity

et al. 2009

View full text Add to dashboard Cite

OBJECTIVE-Based on rodent studies, we examined the hypothesis that increased adipose tissue (AT) mass in obesity without an adequate support of vascularization might lead to hypoxia, macrophage infiltration, and inflammation.RESEARCH DESIGN AND METHODS-Oxygen partial pressure (AT pO 2 ) and AT temperature in abdominal AT (9 lean and 12 overweight/obese men and women) was measured by direct insertion of a polarographic Clark electrode. Body composition was measured by dual-energy X-ray absorptiometry, and insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Abdominal subcutaneous tissue was used for staining, quantitative RT-PCR, and chemokine secretion assay.RESULTS-AT pO 2 was lower in overweight/obese subjects than lean subjects (47 Ϯ 10.6 vs. 55 Ϯ 9.1 mmHg); however, this level of pO 2 did not activate the classic hypoxia targets (pyruvate dehydrogenase kinase and vascular endothelial growth factor [VEGF]). AT pO 2 was negatively correlated with percent body fat (R ϭ Ϫ0.50, P Ͻ 0.05). Compared with lean subjects, overweight/ obese subjects had 44% lower capillary density and 58% lower VEGF, suggesting AT rarefaction (capillary drop out). This might be due to lower peroxisome proliferator-activated receptor ␥1 and higher collagen VI mRNA expression, which correlated with AT pO 2 (P Ͻ 0.05). Of clinical importance, AT pO 2 negatively correlated with CD68 mRNA and macrophage inflammatory protein 1␣ secretion (R ϭ Ϫ0.58, R ϭ Ϫ0.79, P Ͻ 0.05), suggesting that lower AT pO 2 could drive AT inflammation in obesity.CONCLUSIONS-Adipose tissue rarefaction might lie upstream of both low AT pO 2 and inflammation in obesity. These results suggest novel approaches to treat the dysfunctional AT found in obesity. Diabetes 58:718-725, 2009 B oth insulin resistance and ␤-cell failure are present in individuals with type 2 diabetes. Insulin resistance is closely linked to adiposity with a central or visceral pattern, providing a greater risk of insulin resistance and metabolic dysfunction. Adipose tissue (AT) serves as an endocrine organ secreting a variety of autocrine, paracrine, and endocrine factors that can produce or prevent insulin resistance (1). The failure of AT to adequately proliferate and/or differentiate to sequester lipids away from liver, skeletal muscle, and the pancreatic ␤-cell has been proposed as a precursor to type 2 diabetes, broadening the number of potential mechanisms linking obesity to insulin resistance (2).The increase in body fat in obesity should be accompanied by an increase in vascularization, in order to provide adequate oxygen and nutrients (3). In contrast to expectations, obese mice have lower AT capillary density (rarefaction, also known as capillary drop out) and decreased vascular endothelial growth factor (VEGF), the most potent angiogenic factor (4,5). Consistent with this model, preclinical studies suggest that obese AT is hypoxic (6); however, the hypothesis that AT rarefaction might lead to hypoxia remains untested.In humans, short-term whole-body hypoxia decreases i...

show abstract

Section: Discussionsupporting

confidence: 58%

Reduced Adipose Tissue Oxygenation in Human Obesity

et al. 2009

View full text Add to dashboard Cite

show abstract

“…In contrast, LC-n-3 PUFA effects confined to EAT exhibited a predominantly proinflammatory gene expression signature, and the T cell reduction in splenic white pulps of HF/n-3 mice disclose immunosuppressive effects. These observed differences regarding changes in inflammatory state challenge the current perception that LCn-3 PUFA act solely anti-inflammatory (26,69). However, these apparently opposing LC-n-3 PUFA effects may also be a consequence of different background diets applied.…”

Section: Discussionmentioning

confidence: 44%

“…However, it is also known that different fatty acids modulate obesity-related complications differentially in terms of the development of insulin resistance and type 2 diabetes (4,14). Moreover, extreme ratios of LC-n-6 PUFA (e.g., arachidonic acid) to LC-n-3 PUFA [e.g., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] of up to 200:1 have been used (26), whereas human diets have more balanced n-6 PUFA/n-3 PUFA ratios of 17:1 to 1:1 (63). In contrast to LC-n-6 PUFA, it has been reported frequently that LC-n-3 PUFA exert anti-inflammatory actions in the context of cardiovascular diseases and adipose tissue inflammation and seem to possess antiadipogenic effects (57).…”

mentioning

confidence: 99%

Metabolic and immunomodulatory effects of n-3 fatty acids are different in mesenteric and epididymal adipose tissue of diet-induced obese mice

Ludwig

Worsch

Heikenwälder

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…In contrast to similar studies with rodents (209,210) and human subjects (211,212) , these authors, as well as Kratz et al (213) in a study with human subjects, failed to obtain any effect on adipose tissue mass in the pig model (21) . Also, a correlation between the caecal content of Bacteroides spp.…”

Section: Obesitymentioning

confidence: 50%

Use of pigs as a potential model for research into dietary modulation of the human gut microbiota

2013

View full text Add to dashboard Cite

The human intestinal microbial ecosystem plays an important role in maintaining health. A multitude of diseases including diarrhoea, gastrointestinal inflammatory disorders, such as necrotising enterocolitis (NEC) of neonates, and obesity are linked to microbial composition and metabolic activity. Therefore, research on possible dietary strategies influencing microbial composition and activity, both preventive and curative, is being accomplished. Interest has focused on pre-and probiotics that stimulate the intestinal production of beneficial bacterial metabolites such as butyrate, and beneficially affect microbial composition. The suitability of an animal model to study dietary linked diseases is of much concern. The physiological similarity between humans and pigs in terms of digestive and associated metabolic processes places the pig in a superior position over other non-primate models. Furthermore, the pig is a human-sized omnivorous animal with comparable nutritional requirements, and shows similarities to the human intestinal microbial ecosystem. Also, the pig has been used as a model to assess microbiota -health interactions, since pigs exhibit similar syndromes to humans, such as NEC and partly weanling diarrhoea. In contrast, when using rodent models to study diet -microbiota -health interactions, differences between rodents and humans have to be considered. For example, studies with mice and human subjects assessing possible relationships between the composition and metabolic activity of the gut microbiota and the development of obesity have shown inconsistencies in results between studies. The present review displays the similarities and differences in intestinal microbial ecology between humans and pigs, scrutinising the pig as a potential animal model, with regard to possible health effects.

show abstract

Prevention of high-fat diet-induced adipose tissue remodeling in obese diabetic mice by n-3 polyunsaturated fatty acids

Cited by 129 publications

References 69 publications

Reduced Adipose Tissue Oxygenation in Human Obesity

Reduced Adipose Tissue Oxygenation in Human Obesity

Metabolic and immunomodulatory effects of n-3 fatty acids are different in mesenteric and epididymal adipose tissue of diet-induced obese mice

Use of pigs as a potential model for research into dietary modulation of the human gut microbiota

Contact Info

Product

Resources

About