Yuri Takamine

Zinc transporter ZIP13 suppresses beige adipocyte biogenesis and energy expenditure by regulating C/EBP-β expression

Given the relevance of beige adipocytes in adult humans, a better understanding of the molecular circuits involved in beige adipocyte biogenesis has provided new insight into human brown adipocyte biology. Genetic mutations in SLC39A13/ZIP13, a member of zinc transporter family, are known to reduce adipose tissue mass in humans; however, the underlying mechanisms remains unknown. Here, we demonstrate that the Zip13-deficient mouse shows enhanced beige adipocyte biogenesis and energy expenditure, and shows ameliorated diet-induced obesity and insulin resistance. Both gain- and loss-of-function studies showed that an accumulation of the CCAAT/enhancer binding protein-β (C/EBP-β) protein, which cooperates with dominant transcriptional co-regulator PR domain containing 16 (PRDM16) to determine brown/beige adipocyte lineage, is essential for the enhanced adipocyte browning caused by the loss of ZIP13. Furthermore, ZIP13-mediated zinc transport is a prerequisite for degrading the C/EBP-β protein to inhibit adipocyte browning. Thus, our data reveal an unexpected association between zinc homeostasis and beige adipocyte biogenesis, which may contribute significantly to the development of new therapies for obesity and metabolic syndrome.

Body temperature elevation during exercise is essential for activating the Akt signaling pathway in the skeletal muscle of type 2 diabetic rats

This study examined the effect of changes in body temperature during exercise on signal transduction-related glucose uptake in the skeletal muscle of type 2 diabetic rats. Otsuka Long-Evans Tokushima Fatty rats (25 weeks of age), which have type 2 diabetes, were divided into the following four weight-matched groups; control (CON, n = 6), exercised under warm temperature (WEx, n = 8), exercised under cold temperature (CEx, n = 8), and heat treatment (HT, n = 6). WEx and CEx animals were subjected to running on a treadmill at 20 m/min for 30 min under warm (25°C) or cold (4°C) temperature. HT animals were exposed to single heat treatment (40–41°C for 30 min) in a heat chamber. Rectal and muscle temperatures were measured immediately after exercise and heat treatment, and the gastrocnemius muscle was sampled under anesthesia. Rectal and muscle temperatures increased significantly in rats in the WEx and HT, but not the CEx, groups. The phosphorylation levels of Akt, AS160, and TBC1D1 (Thr590) were significantly higher in the WEx and HT groups than the CON group (p < 0.05). In contrast, the phosphorylation levels of AMP-activated protein kinase, ACC, and TBC1D1 (Ser660) were significantly higher in rats in the WEx and CEx groups than the CON group (p < 0.05) but did not differ significantly between rats in the WEx and CEx groups. Body temperature elevation by heat treatment did not activate the AMPK signaling. Our data suggest that body temperature elevation during exercise is essential for activating the Akt signaling pathway in the skeletal muscle of rats with type 2 diabetic rats.

Effects of voluntary running exercise on bone histology in type 2 diabetic rats

The incidence of obesity in children and adolescents, which may lead to type 2 diabetes, is increasing. Exercise is recommended to prevent and improve diabetes. However, little is known about the bone marrow environment at the onset of diabetes in the young, and it is unclear whether exercise training is useful for maintaining bone homeostasis, such as mechanical and histological properties. Thus, this study clarified the histological properties of bone and whether exercise contributes to maintaining bone homeostasis at the onset of type 2 diabetes in rats. Four-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF; n = 21) rats as a diabetic model and Long-Evans Tokushima Otsuka (LETO; n = 18) rats as a control were assigned randomly to four groups: the OLETF sedentary group (O-Sed; n = 11), OLETF exercise group (O-Ex; n = 10), LETO sedentary group (L-Sed; n = 9), and LETO exercise group (L-Ex; n = 9). All rats in the exercise group were allowed free access to a steel running wheel for 20 weeks (5–25 weeks of age). In the glucose tolerance test, blood glucose level was higher in the O-Sed group than that in the L-Sed and L-Ex groups, and was markedly suppressed by the voluntary running exercise of O-Ex rats. The energy to fracture and the two-dimensional bone volume at 25 weeks of age did not differ significantly among the groups, though the maximum breaking force and stiffness were lower in OLETF rats. However, bone marrow fat volume was greater in O-Sed than that in L-Sed and L-Ex rats, and was markedly suppressed by wheel running in the O-Ex rats. Our results indicate that exercise has beneficial effects not only for preventing diabetes but also on normal bone remodeling at an early age.