Consuming a high-fat diet may send the immune system into over-drive, causing it to react more strongly to systemic bacterial infection and leading to inflammation, according to a new study with mice.
Sepsis is medical condition whereby the whole body becomes inflamed. It is characterized by a rapid heart rate, fever, and characterised by tachycardia, fever and a raised white blood cell count. In sever cases it can lead to refractory hypotension and multiple organ failure.
In the United States, incidence of sepsis more than tripled between 1979 and 2000. Mortality from sepsis in the general population is 28.6 per cent, which the researchers behind the new study said is “unacceptably high”. But in obese people it is even higher – around seven tomes so.
Researchers from Louisiana State University’s Health Sciences Center set out to investigate the potential role of the high fat Western diet in this phenomenon. For three weeks they fed groups of mice either a purified control diet or a ‘Western Diet’ (WD) that was enriched with butter fat making up 34.4 per cent of calories. They then caused hepatic inflammation in mice via cecal ligation and puncture (CPL).
They found that the high fat diet enhanced evidence of toll-like receptor (TLR) signalling, and that this pathway also mediates the hepatic response to invading bacteria. This led them to hypothesise that the combined effects of sepsis and the WD on TRL-4 signalling would exacerbate inflammation.
“Feeding WD increased firm adhesion of leukocytes in the sinusoids and terminal
hepatic venules by 8-fold six hours after CLP; the increase in platelet adhesion was
similar to the response observed with leukocytes,” they wrote in the open-access journal BMC Physiology. “Adhesion was accompanied by enhanced expression of TNF-α, MCP-1 and ICAM-1. Messenger RNA expression of TLR-4 was also exacerbated in the WD+CLP group.
“Exposure of C3A cells to PA up-regulated IL-8 and TLR-4 expression. In addition, PA stimulated the static - 3 - adhesion of U937 monocytes to C3A cells, a phenomenon blocked by inclusion of an anti-TLR-4/MD2 antibody in the culture medium.”
The findings led the researchers to conclude that there may be a link between obesity-enhanced susceptibility to sepsis and consumption of a western-style diet.
Lead researcher Chantal Rivera said: "These results suggest that targeting the TLR signaling pathway as a therapeutic approach to the medical management of sepsis may be especially beneficial in obese patients".
Source
BMC Physiology (in press)
“Western diet enhances hepatic inflammation in mice exposed to cecal ligation and puncture”
Authors: Chantal A Rivera, LaTausha Gaskin, Georg Singer, Jeff Houghton and Monique Allman
Fatty diets linked to sepsis immune overreaction: mouse study
Consuming a high-fat diet may send the immune system into over-drive, causing it to react more strongly to systemic bacterial infection and leading to inflammation, according to a new study with mice.
Sepsis is medical condition whereby the whole body becomes inflamed. It is characterized by a rapid heart rate, fever, and characterised by tachycardia, fever and a raised white blood cell count. In sever cases it can lead to refractory hypotension and multiple organ failure.
In the United States, incidence of sepsis more than tripled between 1979 and 2000. Mortality from sepsis in the general population is 28.6 per cent, which the researchers behind the new study said is “unacceptably high”. But in obese people it is even higher – around seven tomes so.
Researchers from Louisiana State University’s Health Sciences Center set out to investigate the potential role of the high fat Western diet in this phenomenon. For three weeks they fed groups of mice either a purified control diet or a ‘Western Diet’ (WD) that was enriched with butter fat making up 34.4 per cent of calories. They then caused hepatic inflammation in mice via cecal ligation and puncture (CPL).
They found that the high fat diet enhanced evidence of toll-like receptor (TLR) signalling, and that this pathway also mediates the hepatic response to invading bacteria. This led them to hypothesise that the combined effects of sepsis and the WD on TRL-4 signalling would exacerbate inflammation.
“Feeding WD increased firm adhesion of leukocytes in the sinusoids and terminal
hepatic venules by 8-fold six hours after CLP; the increase in platelet adhesion was
similar to the response observed with leukocytes,” they wrote in the open-access journal BMC Physiology. “Adhesion was accompanied by enhanced expression of TNF-α, MCP-1 and ICAM-1. Messenger RNA expression of TLR-4 was also exacerbated in the WD+CLP group.
“Exposure of C3A cells to PA up-regulated IL-8 and TLR-4 expression. In addition, PA stimulated the static - 3 - adhesion of U937 monocytes to C3A cells, a phenomenon blocked by inclusion of an anti-TLR-4/MD2 antibody in the culture medium.”
The findings led the researchers to conclude that there may be a link between obesity-enhanced susceptibility to sepsis and consumption of a western-style diet.
Lead researcher Chantal Rivera said: "These results suggest that targeting the TLR signaling pathway as a therapeutic approach to the medical management of sepsis may be especially beneficial in obese patients".
Source
BMC Physiology (in press)
“Western diet enhances hepatic inflammation in mice exposed to cecal ligation and puncture”
Authors: Chantal A Rivera, LaTausha Gaskin, Georg Singer, Jeff Houghton and Monique Allman