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

Department of Cell & Molecular Physiology, University of North Carolina at Chapel Hill, North Carolina, United States of America.
PLoS ONE (Impact Factor: 3.23). 08/2010; 5(8):e12191. DOI: 10.1371/journal.pone.0012191
Source: PubMed


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.

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    • "This bacterium might disrupt the gut barrier and induce gut inflammation[5]. Therefore, it was proposed that microbiota is necessary for development of intestinal inflammation associated with HFD[4]. It is not yet known how HFDinduced bacterial shift directs inflammation in the gut. "
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    ABSTRACT: Objective: Diet-induced inflammation in the small intestine may represent an early event that precedes and predisposes to obesity and insulin resistance. This is related to decrease of lactobacilli in Peyer's patches (PP) revealed in our previous study. The present study aimed to clarify specific changes of PP Lactobacillus on the strain level and related biological activity. Methods: C57 BL/6 J male mice were fed with either low-fat diet (control [CT]; 10% calories from fat) or high-fat diet (HFD; 50% calories from fat) for 25 wk, and the HFD-fed mice were classified into obesity prone (OP) or obesity resistant (OR) on the basis of their body weight gain. Lactobacillus was isolated from PP using a selective medium. Oxidative resistance and cytokine-inducing effect were analyzed in vitro. Results: We obtained 52, 18, and 22 isolates from CT, OP, and OR mice, respectively. They belonged to 13 different types according to enterobacterial repetitive intergenic consensus sequence-PCR analysis. Lactobacillus reuteri was the most abundant strain, but its abundance in OP mice was much lower than that in CT and OR mice. This strain includes eight subgroups according to genotyping. L. reuteri L3 and L. reuteri L8 were the specific strains found in CT and OP mice, respectively. Oxidative-resistant L. reuteri was much higher in HFD-fed mice. When co-cultured with PP cells, L8 induced higher production of proinflammatory cytokines such as interleukin (IL)-6, IL-12, and tumor necrosis factor-α, whereas L3 induced higher production of an anti-inflammatory cytokine (IL-10). Conclusion: HFD may induce oxidative stress that drives strain selection of Lactobacillus strains, resulting in decreased anti-inflammatory response in PP.
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    • "One possible reason for this varying data could be the presence of varying microbiota offering differentinflammatory potential. Indeed the inflammatory responses reported by Ding et al, were dependent on the presence of bacteria[12]. Alternatively, the whole tissue analyses presented here may not be sensitive enough to pick up highly localized regions of inflammation. "
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    • "Moreover, acetyl- CoA carboxylase and carnitine palmitoyl transferase-1, the downstream targets of phosphor-AMPK in fatty acid oxidation, are both statistically increased[27].3.2. Metabolic endotoxemia involved in the low-grade inflammation of DM Current views suggest that low-grade chronic systemic inflammation contributes to the development of insulin resistance, diabetes, and obesity[31,32]. The increased circulating concentration of plasma lipopolysaccharide (LPS), which is defined as metabolic endotoxemia, is a trigger factor for the maintenance of a low-tone continuous inflammatory state in the host responding to high-fat diets[33,34]. The decreased cecal contents of Bifidobacterium spp upon high-fat diets are significantly and negatively correlated with high portal plasma levels of LPS[35]. "
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