High-Fat Diet: Bacteria Interactions Promote Intestinal Inflammation Which Precedes and Correlates with Obesity and Insulin Resistance in Mouse

By Shengli Ding, M. M. Chi, B. Scull, R. Rigby, Nicole M. J. Schwerbrock, S. Magness, C. Jobin, P. Lund. PLoS ONE, 2010

715 citations recorded by the source corpus.

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.

Subfields: Endocrine and Autonomic Systems, Epidemiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d68da401448604358cc9f994842cc42711e7d5c5

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In Endocrine and Autonomic Systems

Liping Zhao

In Epidemiology

In Molecular Biology

Citations in the corpus

High Fat Diet-Induced Gut Microbiota Exacerbates Inflammation and Obesity in Mice via the TLR4 Signaling Pathway (2012, background): “Moreover, this increase in TNFa preceded obesity [16].”
Dietary Polyphenols Promote Growth of the Gut Bacterium Akkermansia muciniphila and Attenuate High-Fat Diet–Induced Metabolic Syndrome (2015, background): “GP Counteract HFD-Induced Effects in the Gastrointestinal Tract Interaction between the gut microbiota and HFD was reported to promote expression of proinflammatory cytokines in intestinal tissues before development of obesity and insulin resistance (4,5).”
Impacts of Gut Bacteria on Human Health and Diseases (2015, background): “reported to be thinner and did not become adipose when subjected to high-fat diet [66].”
Oxidative Stress in Obesity: A Critical Component in Human Diseases (2014, background): “, metabolic syndrome, diabetes mellitus, cardiovascular and liver diseases, and cancer) [2], all-cause mortality, and a reduced life expectancy [150].”
An opportunistic pathogen isolated from the gut of an obese human causes obesity in germfree mice (2012, methodology): “As a step forward, our study has followed a procedure modified from Koch’s Postulates (Evans, 1976) and, for the first time, established a gnotobiotic-mouse obesity model combining HFD with a human-originated endotoxin producer.”
Negative Effects of a High-Fat Diet on Intestinal Permeability: A Review. (2019, background): “This same group also revealed that transplantation of bacteria from HFD mice to germ-free mice resulted in elevated intestinal Nfkb1 expression, indicating that the presence of diet-induced dysbiosis alone is sufficient for inflammation (150).”