Voluntary exercise prevents colonic inflammation in high-fat diet-induced obese mice by up-regulating PPAR-γ activity.

Obesity is associated with increased colonic inflammation, which elevates the risk of colon cancer. Although exercise exerts anti-inflammatory actions in multiple chronic diseases associated with inflammation, it is unknown whether this strategy prevents colonic inflammation in obesity. We hypothesized that voluntary exercise would suppress colonic inflammation in high-fat diet (HFD)-induced obesity by modulation of peroxisome proliferator-activated receptor (PPAR)-γ. Male C57Bl/6J mice fed either a control diet (6.5% fat, CON) or a high-fat diet (24% fat, HFD) were divided into sedentary, voluntary exercise or voluntary exercise with PPAR-γ antagonist GW9662 (10 mg/kg/day). All interventions took place for 12 weeks. Compared with CON-sedentary group, HFD-sedentary mice gained significantly more body weight and exhibited metabolic disorders. Molecular studies revealed that HFD-sedentary mice had increased expression of inflammatory mediators and activation of nuclear factor (NF)-κB in the colons, which were associated with decreased expression and activity of PPAR-γ. Voluntary exercise markedly attenuated body weight gain, improved metabolic disorders, and normalized the expression of inflammatory mediators and activation of NF-κB in the colons in HFD-mice while having no effects in CON-animals. Moreover, voluntary exercise significantly increased expression and activity of PPAR-γ in the colons in both HFD- and CON-animals. However, all of these beneficial effects induced by voluntary exercise were abolished by GW9662, which inhibited expression and activity of PPAR-γ. The results suggest that decreased PPAR-γ activity in the colon of HFD-induced obesity may facilitate the inflammatory response and colon carcinogenesis. Voluntary exercise prevents colonic inflammation in HFD-induced obesity by up-regulating PPAR-γ activity.

[PMP22 mutation of an infant-onset Charcot-Marie-Tooth disease family].

OBJECTIVE: To study the mutation of PMP22 gene of an early-onset family with Charcot-Marie-Tooth disease (CMT) and the genetic features of the disease. METHODS: Two patients with CMT, fifteen unaffected members in the family and 20 healthy controls were enrolled. STR-PCR and gene scanning were used to detect PMP22 duplication mutation. RESULTS: The mutations of PMP22 were found in the two patients and other five unaffected members in the family. The mutations were located in the STR locus D17S921 in 5 cases and in the STR locus D17S4A in 2 cases. The other members in the family and 20 healthy controls did not show the mutations of PMP22. CONCLUSIONS: The gene causing CMT in the family is found in the 17p11.2-p12 region containing PMP22 gene duplication mutation, resulting in the subtype CMT1A.