Alogliptin improves survival and health of mice on a high‐fat diet

Abstract

Alogliptin is a commonly prescribed drug treating patients with type 2 diabetes. Here, we show that long‐term intervention with alogliptin (0.03% w/w in diet) improves survival and health of mice on a high‐fat diet. Alogliptin intervention takes beneficial effects associated with longevity, including increased insulin sensitivity, attenuated functionality decline, decreased organ pathology, preserved mitochondrial function, and reduced oxidative stress. Autophagy activation is proposed as an underlying mechanism of these beneficial effects. We conclude that alogliptin intervention could be considered as a potential strategy for extending lifespan and healthspan in obesity and overweight.

Serine Phosphorylation of IRS1 Correlates with Aβ-Unrelated Memory Deficits and Elevation in Aβ Level Prior to the Onset of Memory Decline in AD

“…In contrast to DIO mice at 45 weeks of age, the phosphorylation of IRS1 at mSer307, which increases in insulin resistance, diabetes, and obesity [5], with phosphorylation at mSer1097 significantly increased in the hippocampus of DIO mice at 35 weeks of age, although there were no significant differences in phosphorylation at mSer612 and mSer632/635 between DIO and age-matched WT mice (Figure 1E, Figure S4A). Consistent with previous studies [27,28], the basal phosphorylation level of p70S6K slightly but significantly increased in the hippocampus of middle-aged DIO mice compared with that in the hippocampus of age-matched WT mice, whereas the basal phosphorylation of Akt and GSK3β and activation of AMPK and atypical protein kinase C ζ/λ (aPKC ζ/λ), downstream factors of insulin signaling, in the hippocampus were comparable between middle-aged WT and DIO mice (Figure 1F, Figures S3A, S4B and S5A). Additionally, the basal phosphorylation of JNK, an inflammation- and stress-related factor, remained unchanged in the hippocampus between the two groups (Figures S3A and S5A), although a relationship between the phosphorylation of IRS1 at mSer307 and activation of these factors in yeast cells, culture cells, and muscles has been reported [5].…”

“…HFD and genetically obese animals exhibit increased phosphorylation at mSer307 and p70S6K-induced phosphorylation at mSer1097 in peripheral tissues [37,38]. In the central nervous system, the involvement of non-activated AMPK with/without phosphorylation of IRS1 at mSer307 accompanied by p70S6K activation or different combinations of alterations in Akt and GSK3β activity (i.e., increased or decreased phosphorylation) in cognitive impairment in 40–45% HFD-fed and STZ mice has been reported [21,22,27,28,32,34,39,40], whereas the monotonous levels of phosphorylation of IRS1 at Ser sites and of downstream kinases including Akt, AMPK, GSK3β, and p70S6K are observed in 45% HFD-induced cognitive deficits [41]. Consistent with these results, memory decline in middle-aged DIO mice is accompanied by a concomitant increase in the basal phosphorylation of IRS1 at mSer307 and mSer1097 with p70S6K activation and monotonous activity of Akt, GSK3β, and AMPK in the hippocampus.…”

Myeloid-derived growth factor inhibits inflammation and alleviates endothelial injury and atherosclerosis in mice

“…From 4 to 6 weeks of age, the mice were fed NCD or WD (40% kcal fat, 43% kcal carbohydrates, and 17% kcal protein; Beijing Hfk Bioscience Co. Ltd., Beijing, China) until the end of the experiment. Body weight, food intake, blood pressure, fecal output, and lipid content in fecal were measured weekly as our previous study ( 27 ). At the terminal of the study, mice were fasted overnight and then anesthetized by intraperitoneal injection of pentobarbital sodium (60 mg/kg) and euthanized for blood and tissue samples.…”

“…Blood pressure values were averaged from three consecutive measurements under steady-state conditions. Food intake, fecal output, and lipid content in feces were measured as previously described ( 27 ).…”

Myeloid‐derived growth factor (MYDGF) protects bone mass through inhibiting osteoclastogenesis and promoting osteoblast differentiation

“…Real‐time PCR were performed as previously described (Mei et al , 2016; Zhu et al , 2019). The primers designed for each targeted gene are listed in Appendix Table S4.…”