High-fat diet: bacteria interactions promote intestinal inflammation which precedes and correlates with obesity and insulin resistance in mouse

• Published in: PloS one 2010-08, Vol.5 (8), p.e12191-e12191
• Main Authors: Ding, Shengli, Chi, Michael M, Scull, Brooks P, Rigby, Rachael, Schwerbrock, Nicole M J, Magness, Scott, Jobin, Christian, Lund, Pauline K
• Format: Article
• Language: English
• Subjects: Activation; Adipose tissue; Adipose Tissue - metabolism; Animal experimentation; Animals; Bacteria; Biomarkers - metabolism; Body Weight; Body weight gain; Diabetes and Endocrinology/Type 2 Diabetes; Diet; Dietary Fats; Diets; Digestive tract; Endothelial cells; Epithelial cells; Gastroenterology and Hepatology/Gastrointestinal Infections; Gastroenterology and Hepatology/Small Intestine; Gene Expression Regulation; Germfree; Glucose; Gnotobiotics; High fat diet; Immune system; Inflammation; Inflammation - complications; Inflammation - metabolism; Inflammation - microbiology; Inflammation - pathology; Insulin; Insulin Resistance; Intestines - metabolism; Intestines - microbiology; Low fat; Low fat diet; Mice; Mice, Inbred C57BL; Microbial drug resistance; Microbiota (Symbiotic organisms); mRNA; NF-kappa B - metabolism; Nutrient deficiency; Nutrition/Obesity; Obesity; Obesity - complications; Obesity - metabolism; Obesity - microbiology; Obesity - pathology; Reporter gene; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Slurries; Small intestine; Specific Pathogen-Free Organisms; Tumor necrosis factor- alpha; Tumor necrosis factor-a; Tumor Necrosis Factor-alpha - genetics; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Type 2 diabetes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0012191

Obesity induced by high fat (HF) diet is associated with inflammation which contributes to development of insulin resistance. Most prior studies have focused on adipose tissue as the source of obesity-associated inflammation. Increasing evidence links intestinal bacteria to development of diet-induced obesity (DIO). This study tested the hypothesis that HF western diet and gut bacteria interact to promote intestinal inflammation, which contributes to the progression of obesity and insulin resistance. Conventionally raised specific-pathogen free (CONV) and germ-free (GF) mice were given HF or low fat (LF) diet for 2-16 weeks. Body weight and adiposity were measured. Intestinal inflammation was assessed by evaluation of TNF-alpha mRNA and activation of a NF-kappaB(EGFP) reporter gene. In CONV but not GF mice, HF diet induced increases in body weight and adiposity. HF diet induced ileal TNF-alpha mRNA in CONV but not GF mice and this increase preceded obesity and strongly and significantly correlated with diet induced weight gain, adiposity, plasma insulin and glucose. In CONV mice HF diet also resulted in activation of NF-kappaB(EGFP) in epithelial cells, immune cells and endothelial cells of small intestine. Further experiments demonstrated that fecal slurries from CONV mice fed HF diet are sufficient to activate NF-kappaB(EGFP) in GF NF-kappaB(EGFP) mice. Bacteria and HF diet interact to promote proinflammatory changes in the small intestine, which precede weight gain and obesity and show strong and significant associations with progression of obesity and development of insulin resistance. To our knowledge, this is the first evidence that intestinal inflammation is an early consequence of HF diet which may contribute to obesity and associated insulin resistance. Interventions which limit intestinal inflammation induced by HF diet and bacteria may protect against obesity and insulin resistance.