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Sepsis is a systemic inflammatory response to infection, with no preventative strategies. In this study, we identify a role for habitual physical activity in the prevention of adipose tissue inflammation induced by a model of sepsis, lipopolysaccharide (LPS). Male C57BL/6J mice (8 weeks old) were housed with access to voluntary wheel running (VWR) or sedentary (SED) for 10 weeks. Mice were then injected with LPS (2 mg/kg) or saline (SAL), and tissues were removed 6 hours postinjection. VWR attenuated body, epididymal adipose tissue (eWAT), and subcutaneous inguinal adipose tissue (iWAT) mass gain, improved glucose tolerance, increased markers of mitochondrial biogenesis in iWAT and eWAT, and increased UCP-1 protein content in iWAT. In iWAT, VWR attenuated the LPS induced increase in mRNA expression of TNF-a, MCP-1, and follistatin, along with phosphorylation of STAT3. In addition, VWR had a main effect for reducing iWAT mRNA expression of IL-1b, IL-6, and SOCS3. In eWAT, VWR had a main effect for reducing mRNA expression of IL-1b, MCP-1, IL-6, and follistatin. Further, VWR increased SOCS3 mRNA expression and phosphorylation of STAT3 in SAL mice, thus the relative change in response to LPS for these markers was attenuated. The protective effect of prior physical activity occurred in conjunction with increases in the protein content of a component of the LPS binding complex, MyD88. Overall, the results from this study demonstrate that habitual physical activity can attenuate the LPS induced inflammatory response in adipose tissue and this occurs to a greater extent in iWAT compare with eWAT.

Peppler WT, Anderson ZG, Sutton CD, Rector RS, Wright DC. Voluntary wheel running attenuates lipopolysaccharide-induced liver inflammation in mice. Am J Physiol Regul Integr Comp Physiol 310: R934 -R942, 2016. First published February 17, 2016 doi:10.1152/ajpregu.00497.2015.-Sepsis induces an acute inflammatory response in the liver, which can lead to organ failure and death. Given the anti-inflammatory effects of exercise, we hypothesized that habitual physical activity could protect against acute sepsis-induced liver inflammation via mechanisms, including heat shock protein (HSP) 70/72. Male C57BL/6J mice (n ϭ 80, ϳ8 wk of age) engaged in physical activity via voluntary wheel running (VWR) or cage control (SED) for 10 wk. To induce sepsis, we injected (2 mg/kg ip) LPS or sterile saline (SAL), and liver was harvested 6 or 12 h later. VWR attenuated increases in body and epididymal adipose tissue mass, improved glucose tolerance, and increased liver protein content of PEPCK (P Ͻ 0.05). VWR attenuated increases in LPS-induced IL-6 signaling and mRNA expression of other inflammatory markers (TNF-␣, chemokine C-C motif ligand 2, inducible nitric oxide synthase, IL-10, IL-1␤) in the liver; however, this was not reflected at the whole body level, as systemic markers of inflammation were similar between SED and VWR. Insulin tolerance was greater in VWR compared with SED at 6 but not 12 h after LPS. The protective effect of VWR occurred in parallel with increases in the liver protein content of HSP70/72, a molecular chaperone that can protect against inflammatory challenges. This study provides novel evidence that physical activity protects against the inflammatory cascade induced by LPS in the liver and that these effects may be mediated via HSP70/72. lipopolysaccharide; inflammation; liver; physical activity; exercise SEPSIS IS A CONTINUUM OF CLINICAL events defined by the presence of infection and systemic inflammation (18). The worldwide incidence of sepsis was recently estimated at 437 cases per 100,000 person years between 2003 and 2015, with an associated fatality rate of 17% (11). This puts a significant burden on the health care system, and in the United States alone, the direct hospital costs associated with sepsis are over $24 billion (17).The infiltration of a host with both gram-negative and gram-positive bacterial species is often considered to be the cause of acute sepsis (34). LPS from Escherichia coli, a component of gram-negative bacteria, is often used to produce these effects in rodent models. Upon exposure to LPS, an inflammatory cascade is activated both systemically and at a tissue-specific level (1). Initial signaling involves a Toll-like receptor 4 (TLR4)-myeloid differentiation primary response gene 88 (MyD88) interaction that then propagates the inflammatory response (24). Increases in circulating inflammatory factors, such as TNF-␣, IL-6, and IL-1␤, occur rapidly and are regulated by the dose and duration of exposure (21,29,40). Clearance of inflammatory markers begins as early as 8 h post...

High-fat diets rapidly cause weight gain and glucose intolerance. We sought to determine whether these changes could be mitigated with prior exercise training. Male C57BL/6J mice were exercise-trained by treadmill running (1 h/day, 5 days/wk) for 4 wk. Twenty-four hours after the final bout of exercise, mice were provided with a high-fat diet (HFD; 60% kcal from lard) for 4 days, with no further exercise. In mice fed the HFD prior to exercise training, the results were blunted weight gain, reduced fat mass, and a slight attenuation in glucose intolerance that was mirrored by greater insulin-induced Akt phosphorylation in skeletal muscle compared with sedentary mice fed the HFD. When ad libitum-fed sedentary mice were compared with sedentary high-fat fed mice that were calorie restricted (-30%) to match the weight gain of the previously trained high-fat fed mice, the same attenuated impairments in glucose tolerance were found. Blunted weight gain was associated with a greater capacity to increase energy expenditure in trained compared with sedentary mice when challenged with a HFD. Although mitochondrial enzymes in white adipose tissue and UCP-1 protein content in brown adipose tissue were increased in previously exercised compared with sedentary mice fed a HFD, ex vivo mitochondrial respiration was not increased in either tissue. Our data suggest that prior exercise training attenuates high-fat diet-induced weight gain and glucose intolerance and is associated with a greater ability to increase energy expenditure in response to a high-fat diet.