Necroptosis, a form of programmed cell death, accounts for many inflammations in a wide range of diseases. Diet-induced obesity is manifested by low-grade inflammation in the mediobasal hypothalamus (MBH), and microglia are implicated as critical responsive components for this process. Here, we demonstrate that microglial necroptosis plays a pivotal role in obesity-related hypothalamic inflammation, facilitating proinflammatory cytokine production, such as TNF-α and IL-1β. Treatment with the anti-diabetic drug metformin effectively reduces the obese phenotypes in the high-fat diet (HFD)-fed mice, attributing to remission of hypothalamic inflammation partly through repressing microglial necroptosis. Importantly, using the receptor-interacting protein kinase 1 inhibitor, necrostatin-1s, could not suppress the microglial inflammation nor prevent body weight gain in the obese mice, indicating that the microglial necroptosis is RIPK1-independent. Altogether, these findings offer new insights into hypothalamic inflammation in diet-induced obesity and provide a novel mechanism of action for metformin in obesity treatment.

Background. The role of physical activity is well-known to intercept the condition of fragility and decrease its outcomes. This study aimed to determine the efficacious physical activity intervention measure which enhances the outcomes associated to fragility in the older adults. Material and Methods. We searched MEDLINE, Cochrane Central Register of Controlled, and EMBASE for the published studies in the duration June 2000 to February 2020 which were further shortlisted as per the inclusion and exclusion criteria of the study. The elder population considered from the selected studies was considered in an age of 65 years or more who were pre-fragile or fragile. Here, we included the clinical as well as randomized control trials. Results. After extracting the data, we measured the risk ratio for aerobic intervention for physical intervention group as 0.55 [95% confidence interval (C.I) as 0.29, 1.03], mobility/rehabilitation interventions were nonsignificant for both groups with reported risk ratio as 1.13 (95% C.I as 0.96, 1.33), muscular strength randomized control trails as a significant integrated outcome estimate over the mobility measure, where the risk ratio was obtained as 1.17 (95% C.I 1.00, 1.35), for the randomized control trials of the mixed interventions showed a significant integrated outcome over the measures of mobility with obtained risk difference 0.03 (95% C.I -0.03, 0.09) and significant effects for daily life activities for intervention group with odds ratio 0.98 (95% C.I was 0.68, 1.41). Conclusion. From the conducted systematic review and meta-analysis, we determined a low to medium authentication that different physical activities interventions are considered to be advantageous for the pre-fragile as well as the fragile elderly people. The studies are required to be more comprehensive and clear about defining the fragility so as to assure the determination and performing of such interventions into a clinical execution.

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