β-aminoisobutyric acid (BAIBA) is produced in skeletal muscle during exercise and has beneficial effects on obesity-related metabolic disorders such as diabetes and non-alcoholic fatty liver disease. Thus, it is supposed to prevent high fat diet (HFD)-induced inflammation and insulin resistance in adipose tissue though anti-inflammatory effects in obesity. Previous reports have also demonstrated strong anti-inflammatory effects of BAIBA. We used BAIBA treated fully differentiated 3T3T-L1 mouse adipocytes to investigate the effects of exogenous BAIBA on inflammation and insulin signaling in adipocytes. Insulin signaling-mediated proteins and inflammation markers were measured by Western blot analysis. Secretion of pro-inflammatory cytokines were measured by ELISA. Lipid accumulation in differentiated 3 T3-L1 cells was stained by Oil red-O. Statistical analysis was performed by ANOVA and student’s t test. BAIBA treatment suppressed adipogenesis assessed by adipogenic markers as well as lipid accumulation after full differentiation. We showed that BAIBA treatment stimulated AMP-activated protein kinase (AMPK) phosphorylation in a dose-dependent manner and lipopolysaccharide (LPS)-induced secretion of pro-inflammatory cytokines such as TNFα and MCP-1 was abrogated in BAIBA-treated 3 T3-L1 cells. Treatment of 3 T3-L1 cells with BAIBA reduced LPS-induced NFκB and IκB phosphorylation. Furthermore, BAIBA treatment ameliorated LPS-induced impairment of insulin signaling measured by IRS-1 and Akt phosphorylation and fatty acid oxidation. Suppression of AMPK by small interfering (si) RNA significantly restored these changes. We demonstrated anti-inflammatory and anti-insulin resistance effects of BAIBA in differentiated 3 T3-L1 cells treated with LPS through AMPK-dependent signaling. These results provide evidence for the beneficial effects of BAIBA not only in liver and skeletal muscle cells but also in adipose tissue.

Secondary lymphedema is an intractable disease mainly caused by damage of the lymphatic system during surgery, yet studies are limited by the lack of suitable animal models. The purpose of this study was to create an improved model of secondary lymphedema in the hindlimbs of rodents with sustained effects and able to mimic human lymphedema. This was achieved by combining previously reported surgical methods and radiation to induce chronic lymphedema. Despite more radical surgical destruction of superficial and deep lymphatic vessels, surgery alone was not enough to sustain increased hindlimb volume. Radiotherapy was necessary to prolong these effects, with decreased lymphatic flow on lymphoscintigraphy, but hindlimb necrosis occurred after 4 weeks due to radiation toxicity. The applicability of this model for studies of therapeutic lymphangiogenesis was subsequently tested by injecting muscle-derived stem cells previously cocultured with the supernatant of human lymphatic endothelial cells in vitro. There was a tendency for increased lymphatic flow which significantly increased lymphatic vessel formation after cell injection, but attenuation of hindlimb volume was not observed. These results suggest that further refinement of the rodent hindlimb model is needed by titration of adequate radiation dosage, while stem cell lymphangiogenesis seems to be a promising approach.

Kim TG, et al. J Korean Med Sci. 2016 Jan;31(1):120-124. http://dx.doi.org/10.3346/jkms.2016.31.1.120