The concept that obesity is an inflammatory state has changed our understanding of this condition and suggested that pharmacological interventions targeting inflammation may be useful strategies to improve metabolic complications of obesity. Phosphodiesterase 4 (PDE4) inhibitors exhibit profound antiinflammatory effects, but whether PDE4 inhibition suppresses obesity-induced inflammation is unknown. Among PDE4 isoforms, PDE4B is the major species mediating inflammatory responses. We therefore examined obesity-related phenotypes in mice deficient for PDE4B. Compared with wild-type littermates, PDE4B-null mice were leaner, with lower fat pad weights, smaller adipocytes, and decreased serum leptin levels on both chow and high-fat diets (HFDs). PDE4B deficiency suppressed TNF-alpha mRNA levels and macrophage infiltration in white adipose tissue in mice on HFD, but insulin sensitivity was unaltered. PDE4B-null mice on HFDs had increased locomotor activity. These results suggest a previously unappreciated role for PDE4B in the regulation of energy balance and that PDE4B inhibitors could have utility in treatment of obesity and for suppression of obesity-induced inflammation in white adipose tissue.

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Aim: To investigate the impact of chronic apical periodontitis (CAP) on atherosclerosis and gut microbiota by establishing a Porphyromonas gingivalis (P. gingivalis)induced CAP in an apolipoprotein E-deficient (apoE −/− ) mice model. Methodology:Twenty-eight male apoE −/− mice were divided into two groups with 14 in each: CAP group and control group. In the CAP group, sterile cotton wool containing 10 8 colony-forming units of P. gingivalis was placed into the pulp chamber after pulp exposure followed by coronal resin filling in bilateral maxillary first and second molars. The mice were fed with a chow diet to induce atherosclerosis. Animals were euthanized 16 weeks after the operation, and the periapical lesions of bilateral maxillary first and second molars were assessed by micro-CT. After collection of aortic arches, atherosclerotic lesions were measured by Oil Red O staining.Serum levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG) were measured. Stools were collected to detect alterations in gut microbiota by 16S rRNA gene sequencing. Independent samples t-test was used to calculate the difference between the two groups. Results: CAP was observed in 98.2% of molars. A significant increase in atherosclerotic plaque formation in the aortic arches was found in the CAP groups (CAP: 2.001% ± 0.27%, control: 0.927% ± 0.22%, p = .005). No significant difference was observed between sevum level of HDL-C (CAP: 2.295 ± 0.

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