Intestinal, adipose, and liver inflammation in diet-induced obese mice.
Chronic inflammation and increased visceral adipose tissue (VAT) are key elements of the metabolic syndrome. Both are considered to play a pathogenic role in the development of liver steatosis and insulin resistance. The aim of the present study was to investigate the hypothesis that an inflamed intestine, induced both by diet and chemical irritation, could induce persistent inflammation in VAT. Female C57BL/6JOlaHsd mice were used. In study I, groups of mice (n = 6 per group) were given an obesity-inducing cafeteria diet (diet-induced obesity) or regular chow only (control) for 14 weeks. In study II, colitis in mice (n = 8) was induced by 3% dextran sulfate sodium in tap water for 5 days followed by 21 days of tap water alone. Healthy control mice (n = 8) had tap water only. At the end of the studies, all mice were killed; and blood and tissues were sampled and processed for analysis. Body weight of diet-induced obese mice was greatly increased, with evidence of systemic inflammation, insulin resistance, and liver steatosis. Tissue inflammation indexed by proinflammatory cytokine expression was recorded in liver, mesenteric fat, and proximal colon/distal ileum, but not in subcutaneous or perigonadal fat. In dextran sulfate sodium-induced colitis mice, mesenteric fat was even more inflamed than the colon, whereas a much milder inflammation was seen in liver and subcutaneous fat. The studies showed both diet- and colitis-initiated inflammation in mesenteric fat. Fat depots contiguous with intestine and their capacity for exaggerated inflammatory responses to conditions of impaired gut barrier function may account for the particularly pathogenic role of VAT in obesity-induced metabolic disorders.
Li
Hong
H
Department of Integrative Pharmacology, AstraZeneca R&D Mölndal, S-431 83 Mölndal, Sweden.
Lelliott
Christopher
C
Håkansson
Pernilla
P
Ploj
Karolina
K
Tuneld
Anna
A
Verolin-Johansson
Martina
M
Benthem
Lambertus
L
Carlsson
Björn
B
Storlien
Leonard
L
Michaëlsson
Erik
E
D000818:Animals; D001835:Body Weight / Q000502:physiology; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004036:Diet, Atherogenic; D005260:Female; D005759:Gastroenteritis / Q000097:blood / Q000150:complications* / Q000473:pathology / Q000662:veterinary; D006520:Hepatitis, Animal / Q000097:blood / Q000150:complications* / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D050152:Intra-Abdominal Fat / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000150:complications* / Q000209:etiology / Q000473:pathology / Q000662:veterinary; D009929:Organ Size; D015436:Panniculitis, Peritoneal / Q000097:blood / Q000150:complications* / Q000473:pathology / Q000662:veterinary
D016207:Cytokines