Brown adipocytes have a thermogenic function and are involved in maintaining body temperature when cold, regulating energy consumption and metabolism. These functions are attracting attention as therapeutic targets for obesity and associated metabolic diseases. Deficiency of MAPK regulated corepressor interacting protein 2 (MCRIP2), a highly expressed gene in brown adipocytes, attenuated cold tolerance in mice. Cellular knockdown of Mcrip2 in brown adipocytes had no apparent effect on the differentiation of progenitor cells to mature cells. On the other hand, expressions of mitochondria-related genes and mitochondrial glycolysis were both significantly reduced. Taken together, these observations suggest that MCRIP2 plays an important role in maintaining normal mitochondrial function.

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Systemic chemotherapies have proven to be effective for treating esophageal squamous cell carcinoma (ESCC). In advanced ESCC, predicting the response to primary chemotherapy is critical. In this study, we investigated the relationship between NFE2L2 gene status and chemotherapy response in ESCC patients. A sequence analysis of 61 primary ESCCs revealed that 13 (21.3%) had mutations in NFE2L2. Among the 50 ESCC patients who received primary chemotherapy, objective response rate of patients with NFE2L2 mutation (2/8, 25.0%) was significantly lower than that of patients with NFE2L2 wild type (30/42, 71.4%) (p = 0.02, Fisher’s exact test). Furthermore, among 43 patients who received triplet chemotherapy with docetaxel, cisplatin, and 5-FU, NFE2L2 mutant patients (n = 5) had a significantly lower overall survival rate than NFE2L2 wildtype patients (n = 38, p = 0.03, Log-rank test). NFE2L2 mutations were also found in 4 of 11 (36.4%) ESCC cell lines. The rate of growth inhibition by anticancer drugs in NFE2L2 mutant cells was significantly lower than in wildtype cells (p < 0.01, Mann–Whitney U test). Our findings suggest that NFE2L2 status can predict chemotherapy response in patients with ESCC.

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Exercise increases the levels of brain-derived neurotrophic factor (BDNF), which is beneficial in glucose metabolism. The combined effect of the single nucleotide polymorphism (SNP) in BDNF (rs6265; G to A, Val66Met) and physical activity (PA) on the effectiveness of dipeptidyl peptidase-4 inhibitors (DPP-4Is) was studied in 173 patients with type 2 diabetes. DPP-4I nonresponse was defined as less than 0.2% decrease in HbA1c level 3–4 months after treatment initiation. PA was retrospectively estimated using the International Physical Activity Questionnaire. In patients categorized according to the SNP status and the median PA level, the non-responder rates in the G/* with lower PA, G/^* with higher PA, A/A with lower PA, and A/A with higher PA groups were 40.0%, 26.3%, 18.2%, and 9.1%, respectively, in the entire cohort (p = 0.083), and 56.8%, 28.6%, 25.0%, and 20.0%, respectively, after the exclusion of metformin-treated patients (n = 99, p = 0.037). These findings were sustained in the multivariate model. PA seems more important for responsiveness to DPP-4Is in G/^* patients with activity-dependent BDNF secretion than in A/A patients who are expected to be defective in such secretion, but several limitations exist and further investigation is warranted to conclude this issue.

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