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

被引:510
作者
Ding, Shengli [1 ,2 ]
Chi, Michael M. [1 ,2 ]
Scull, Brooks P. [3 ]
Rigby, Rachael [4 ]
Schwerbrock, Nicole M. J. [1 ,2 ]
Magness, Scott [5 ]
Jobin, Christian [1 ,2 ]
Lund, Pauline K. [1 ,2 ]
机构
[1] Univ N Carolina, Dept Cell & Mol Physiol, Chapel Hill, NC 27515 USA
[2] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA
[3] Vanderbilt Univ, Dept Gastroenterol, Med Ctr, Nashville, TN USA
[4] Univ Lancaster, Sch Hlth & Med, Div Biomed & Life Sci, Lancaster, England
[5] Univ N Carolina, Div Gastroenterol & Hepatol, Dept Med, Chapel Hill, NC USA
来源
PLOS ONE | 2010年 / 5卷 / 08期
关键词
NECROSIS-FACTOR-ALPHA; ADIPOSE-TISSUE; TNF-ALPHA; HEPATIC STEATOSIS; GUT MICROBIOTA; KAPPA-B; MECHANISMS; MICE; JNK;
D O I
10.1371/journal.pone.0012191
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-alpha mRNA and activation of a NF-kappa B-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-kappa B-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-kappa B-EGFP in GF NF-kappa B-EGFP 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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页数:13
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共 33 条
[1]   Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action [J].
Aguirre, V ;
Werner, ED ;
Giraud, J ;
Lee, YH ;
Shoelson, SE ;
White, MF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (02) :1531-1537
[2]   IKK-β links inflammation to obesity-induced insulin resistance [J].
Arkan, MC ;
Hevener, AL ;
Greten, FR ;
Maeda, S ;
Li, ZW ;
Long, JM ;
Wynshaw-Boris, A ;
Poli, G ;
Olefsky, J ;
Karin, M .
NATURE MEDICINE, 2005, 11 (02) :191-198
[3]   The gut microbiota as an environmental factor that regulates fat storage [J].
Bäckhed, F ;
Ding, H ;
Wang, T ;
Hooper, LV ;
Koh, GY ;
Nagy, A ;
Semenkovich, CF ;
Gordon, JI .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (44) :15718-15723
[4]   Mechanisms underlying the resistance to diet-induced obesity in germ-free mice [J].
Backhed, Fredrik ;
Manchester, Jill K. ;
Semenkovich, Clay F. ;
Gordon, Jeffrey I. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (03) :979-984
[5]   Mechanisms of disease - Nuclear factor-kappa b - A pivotal transcription factor in chronic inflammatory diseases [J].
Barnes, PJ ;
Larin, M .
NEW ENGLAND JOURNAL OF MEDICINE, 1997, 336 (15) :1066-1071
[6]  
BGREENBERG AS, 2006, J CLIN NUTR S, V86, pS461
[7]   ICAM-1 expression in adipose tissue: effects of diet-induced obesity in mice [J].
Brake, Danett K. ;
Smith, E. O'Brian ;
Mersmann, Harry ;
Smith, C. Wayne ;
Robker, Rebecca L. .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2006, 291 (06) :C1232-C1239
[8]   Role of gut microflora in the development of obesity and insulin resistance following high-fat diet feeding [J].
Cani, P. D. ;
Delzenne, N. M. ;
Amar, J. ;
Burcelin, R. .
PATHOLOGIE BIOLOGIE, 2008, 56 (05) :305-309
[9]   Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability [J].
Cani, P. D. ;
Possemiers, S. ;
Van de Wiele, T. ;
Guiot, Y. ;
Everard, A. ;
Rottier, O. ;
Geurts, L. ;
Naslain, D. ;
Neyrinck, A. ;
Lambert, D. M. ;
Muccioli, G. G. ;
Delzenne, N. M. .
GUT, 2009, 58 (08) :1091-1103
[10]   Metabolic endotoxemia initiates obesity and insulin resistance [J].
Cani, Patrice D. ;
Amar, Jacques ;
Iglesias, Miguel Angel ;
Poggi, Marjorie ;
Knauf, Claude ;
Bastelica, Delphine ;
Neyrinck, Audrey M. ;
Fava, Francesca ;
Tuohy, Kieran M. ;
Chabo, Chantal ;
Waget, Aurelie ;
Delmee, Evelyne ;
Cousin, Beatrice ;
Sulpice, Thierry ;
Chamontin, Bernard ;
Ferrieres, Jean ;
Tanti, Jean-Francois ;
Gibson, Glenn R. ;
Casteilla, Louis ;
Delzenne, Nathalie M. ;
Alessi, Marie Christine ;
Burcelin, Remy .
DIABETES, 2007, 56 (07) :1761-1772