Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation

Serre, Claire B. de La; Ellis, Collin L.; Lee, Jennifer; Hartman, Amber; Rutledge, John C.; Raybould, Helen E.

doi:10.1152/ajpgi.00098.2010

Cited by 808 publications

(731 citation statements)

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“…As described previously (13,24,25), these rats carry either a polygenic susceptibility (DIO) or resistance (DR) to obesity. After 8 wk on a HF diet, DR rats maintained a body weight similar to control rats fed a LF diet, whereas DIO rats had significantly greater body weight.…”

Section: Discussionmentioning

confidence: 99%

“…Consumption of a HF diet has also been found to increase plasma LPS levels (11,13). Chronic low-dose LPS infusion in mice fed laboratory chow resulted in increased body weight and inflammation (11).…”

Section: Discussionmentioning

confidence: 99%

“…Given that VAN play a major role in the regulation of meal size and duration and express leptin receptors, we hypothesized that leptin resistance could also occur in VAN in diet-induced obesity. The specific aims of the current study were to determine 1) whether leptin resistance occurs in VAN from obese rats by measuring phosphorylation of STAT3 both in vivo following exogenous leptin administration and in vitro by exposure of VAN in short-term culture to leptin and 2) the possible mechanism of leptin resistance in VAN, focusing specifically on the microbial breakdown product lipopolysaccharide (LPS), found to be upregulated in obese animals (11,13) and to increase SOCS-3 expression (33).…”

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Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons

Lartigue

Serre

Espero

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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de Lartigue G, Barbier de la Serre C, Espero E, Lee J, Raybould HE. Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons. Am J Physiol Endocrinol Metab 301: E187-E195, 2011. First published April 26, 2011; doi:10.1152/ajpendo.00056.2011.-Ingestion of high-fat, high-calorie diets is associated with hyperphagia, increased body fat, and obesity. The mechanisms responsible are currently unclear; however, altered leptin signaling may be an important factor. Vagal afferent neurons (VAN) integrate signals from the gut in response to ingestion of nutrients and express leptin receptors. Therefore, we tested the hypothesis that leptin resistance occurs in VAN in response to a high-fat diet. Sprague-Dawley rats, which exhibit a bimodal distribution of body weight gain, were used after ingestion of a high-fat diet for 8 wk. Body weight, food intake, and plasma leptin levels were measured. Leptin signaling was determined by immunohistochemical localization of phosphorylated STAT3 (pSTAT3) in cultured VAN and by quantifaction of pSTAT3 protein levels by Western blot analysis in nodose ganglia and arcuate nucleus in vivo. To determine the mechanism of leptin resistance in nodose ganglia, cultured VAN were stimulated with leptin alone or with lipopolysaccharide (LPS) and SOCS-3 expression measured. SOCS-3 protein levels in VAN were measured by Western blot following leptin administration in vivo. Leptin resulted in appearance of pSTAT3 in VAN of low-fat-fed rats and rats resistant to diet-induced obesity but not diet-induced obese (DIO) rats. However, leptin signaling was normal in arcuate neurons. SOCS-3 expression was increased in VAN of DIO rats. In cultured VAN, LPS increased SOCS-3 expression and inhibited leptin-induced pSTAT3 in vivo. We conclude that VAN of diet-induced obese rats become leptin resistant; LPS and SOCS-3 may play a role in the development of leptin resistance.lipopolysaccharide; high-fat diet; suppressor of cytokine signaling-3 THE GUT PLAYS A CRUCIAL ROLE in sensing luminal contents that is important for the efficient digestion and absorption of ingested nutrients but also in integration of other physiological processes that regulate metabolism and energy expenditure, such as pancreatic ␤-cell function, hepatic function, and also food intake (34). In response to the presence or absence of food, enteroendocrine cells of the gut release anorexic or orexigenic hormones, respectively. The first site of integration of these signals occurs at the level of vagal afferent neurons (VAN), which project to and stimulate second-order neurons in the dorsal vagal complex of the hindbrain (27). VAN express receptors for many of the anorexigenic and orexigenic hormones released from the gut wall and mediate changes in gastrointestinal function and food intake in response to luminal nutrients (18).Leptin is a gut and adipose tissue-derived hormone that regulates a range of biological functions and processes, including energy intake and expenditure, body fat, neuroendocrine systems...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons

Lartigue

Serre

Espero

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

154

142

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“…The significance of the protective role of the GM has been highlighted by the profound impact seen when the GM is absent or disrupted. Germ-free mice have poorly developed mucosal architecture and rudimentary development of the mucosa-associated lymphoid tissue, being generally small and underweight, and also highly susceptible to intestinal infection (10) .In obese patients, there is a significant change in the composition of the GM compared with lean controls (11,12) , and, in rats, these modifications can be induced by the ingestion of a HFD (13) . Furthermore, host nutritional status may be markedly influenced by the composition and activities of the GM since the Bacteroidetes:Firmicutes ratio seems to be decreased in obese individuals and genetically obese mice harbour an 'obese microbiome', with a transferable elevated capacity for energy sequestration (14) .…”

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Changes in gut microbiota due to supplemented fatty acids in diet-induced obese mice

et al. 2013

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Consumption of a high-fat diet (HFD), which is associated with chronic 'low-grade' systemic inflammation, alters the gut microbiota (GM). The aim of the present study was to investigate the ability of an oleic acid-derived compound (S1) and a combination of n-3 fatty acids (EPA and DHA, S2) to modulate both body weight and the GM in HFD-induced obese mice. A total of eighty mice were fed either a control diet or a HFD, non-supplemented or supplemented with S1 or S2. At week 19, faeces were collected in order to analyse the GM. Groupspecific primers for accurate quantification of several major bacterial groups from faecal samples were assayed using quantitative PCR. The HFD induced an increase in body weight, which was reduced by supplementation with S1. Furthermore, S1 supplementation markedly increased total bacterial density and restored the proportions of bacteria that were increased (i.e. clostridial cluster XIVa and Enterobacteriales) or decreased (i.e. Bifidobacterium spp.) during HFD feeding. S2 supplementation significantly increased the quantities of Firmicutes (especially the Lactobacillus group). Correlation analysis revealed that body weight correlated positively with the phylum Firmicutes and clostridial cluster XIVa, and negatively with the phylum Bacteroidetes. In conclusion, the consumption of a HFD induced changes in the faecal microbiota, which were associated with the appearance of an obese phenotype. Supplementation of the HFD with S1 counteracted HFD-induced gut dysbiosis, together with an improvement in body weight. These data support a role for certain fatty acids as interesting nutrients related to obesity prevention.Key words: Gut microbiota: Fatty acids: Obese mice: Quantitative PCR The worldwide prevalence of overweight and obesity has increased dramatically in the past decades, reaching epidemic levels (1) . It is well known that a high-fat diet (HFD) leads, especially in genetically predisposed individuals, to an accumulation of adipose tissue (2) and to the development of a cluster of metabolic and cardiovascular disorders such as type 2 diabetes, atherosclerosis, hypertension and stroke (3) .The gut microbiota (GM) has an important role in supplying nutrients and vitamins, giving colonisation resistance against pathogenic bacteria and interacting with the host immune system and intestinal epithelium (4) . The possible involvement of the host genotype, particularly as it relates to immunophenotype, has been frequently postulated as a major influence on GM composition and stability. Other variables known to broadly influence the composition of the GM include the type of delivery (vaginal or caesarean), age, the use of antibiotics and other drugs, and 'lifestyle' (such as diet, physical activity and stress) (5 -9) . The significance of the protective role of the GM has been highlighted by the profound impact seen when the GM is absent or disrupted. Germ-free mice have poorly developed mucosal architecture and rudimentary development of the mucosa-associated lymphoid tissue, b...

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“…As previously studied, obesity may also be associated with gut inflammation (Hotamisligil 2006;de La Serre et al 2010); (ii) Alteration of the microbial activity and metabolism: competing microorganisms are reduced which may spare nutrients and leave them for the host (Feighner and Dashkevicz 1987). Furthermore, there is possibly an attenuated production of important metabolites such as short-chain fatty acids (SCFA) as well as differences in the capacity to metabolize and transport vitamins, bile acid, hormones and cholesterol Chen et al 2014).…”

Section: Strategies To Manipulate Gut Microbiota In Obesity Antibioticsmentioning

confidence: 99%

The art of targeting gut microbiota for tackling human obesity

Aguirre

Venema

2015

Genes Nutr

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Recently, a great deal of interest has been expressed regarding strategies to tackle worldwide obesity because of its accelerated wide spread accompanied with numerous negative effects on health and high costs. Obesity has been traditionally associated with an imbalance in energy consumed when compared to energy expenditure. However, growing evidence suggests a less simplistic event in which gut microbiota plays a key role. Obesity, in terms of microbiota, is a complicated disequilibrium that presents many unclear complications. Despite this, there is special interest in characterizing compositionally and functionally the obese gut microbiota with the help of in vitro, animal and human studies. Considering the gut microbiota as a factor contributing to human obesity represents a tool of great therapeutic potential. This paper reviews the use of antimicrobials, probiotics, fecal microbial therapy, prebiotics and diet to manipulate obesity through the human gut microbiota and reveals inconsistencies and implications for future study.

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Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation

Cited by 808 publications

References 39 publications

Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons

Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons

Changes in gut microbiota due to supplemented fatty acids in diet-induced obese mice

The art of targeting gut microbiota for tackling human obesity

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