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

S Ding, MM Chi, BP Scull, R Rigby, NMJ Schwerbrock… - PloS one, 2010 - journals.plos.org
S Ding, MM Chi, BP Scull, R Rigby, NMJ Schwerbrock, S Magness, C Jobin, PK Lund
PloS one, 2010journals.plos.org
Background 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. Methodology/Principal …
Background
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.
Methodology/Principal Findings
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-α mRNA and activation of a NF-κBEGFP reporter gene. In CONV but not GF mice, HF diet induced increases in body weight and adiposity. HF diet induced ileal TNF-α 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-κBEGFP 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-κBEGFP in GF NF-κBEGFP mice.
Conclusions/Significance
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.
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