Sn-Substituted Argyrodite LiPSCl Solid Electrolyte for Improving Interfacial and Atmospheric Stability.

Sulfide-based solid electrolytes exhibit good formability and superior ionic conductivity. However, these electrolytes can react with atmospheric moisture to generate HS gas, resulting in performance degradation. In this study, we attempted to improve the stability of the interface between Li metal and an argyrodite LiPsCl solid electrolyte by partially substituting P with Sn to form an Sn-S bond.

Mitoribosomal defects aggravate liver cancer via aberrant glycolytic flux and T cell exhaustion.

Background: Mitochondria are involved in cancer energy metabolism, although the mechanisms underlying the involvement of mitoribosomal dysfunction in hepatocellular carcinoma (HCC) remain poorly understood. Here, we investigated the effects of mitoribosomal impairment-mediated alterations on the immunometabolic characteristics of liver cancer.

Methods: We used a mouse model of HCC, liver tissues from patients with HCC, and datasets from The Cancer Genome Atlas (TCGA) to elucidate the relationship between mitoribosomal proteins (MRPs) and HCC.

Skeletal muscle mitoribosomal defects are linked to low bone mass caused by bone marrow inflammation in male mice.

Background: Mitochondrial oxidative phosphorylation (OxPhos) is a critical regulator of skeletal muscle mass and function. Although muscle atrophy due to mitochondrial dysfunction is closely associated with bone loss, the biological characteristics of the relationship between muscle and bone remain obscure. We showed that muscle atrophy caused by skeletal muscle-specific CR6-interacting factor 1 knockout (MKO) modulates the bone marrow (BM) inflammatory response, leading to low bone mass.

Expression of LONP1 Is High in Visceral Adipose Tissue in Obesity, and Is Associated with Glucose and Lipid Metabolism.

Background: The nature and role of the mitochondrial stress response in adipose tissue in relation to obesity are not yet known. To determine whether the mitochondrial unfolded protein response (UPRmt) in adipose tissue is associated with obesity in humans and rodents.

Methods: Visceral adipose tissue (VAT) was obtained from 48 normoglycemic women who underwent surgery.

Th2 Cytokines Increase the Expression of Fibroblast Growth Factor 21 in the Liver.

Interleukin-4 (IL-4) and IL-13 are the major T helper 2 (Th2) cytokines, and they are involved in the regulation of metabolism in the adipose tissue. The liver contains diverse innate and adaptive immune cells, but it remains to be determined whether Th2 cytokines modulate energy metabolism in the liver. Here, using gene expression data from the Gene Expression Omnibus (GEO) and the BXD mouse reference population, we determined that the Th2 cytokines IL-4 and IL-13 increase the secretion of fibroblast growth factor 21 (FGF21) in the liver.

Differential roles of GDF15 and FGF21 in systemic metabolic adaptation to the mitochondrial integrated stress response.

Perturbation of mitochondrial proteostasis provokes cell autonomous and cell non-autonomous responses that contribute to homeostatic adaptation. Here, we demonstrate distinct metabolic effects of hepatic metabokines as cell non-autonomous factors in mice with mitochondrial OxPhos dysfunction. Liver-specific mitochondrial stress induced by a loss-of-function mutation in (LKO) leads to aberrant oxidative phosphorylation and promotes the mitochondrial unfolded protein response.

Growth differentiation factor 15 protects against the aging-mediated systemic inflammatory response in humans and mice.

Mitochondrial dysfunction is associated with aging-mediated inflammatory responses, leading to metabolic deterioration, development of insulin resistance, and type 2 diabetes. Growth differentiation factor 15 (GDF15) is an important mitokine generated in response to mitochondrial stress and dysfunction; however, the implications of GDF15 to the aging process are poorly understood in mammals. In this study, we identified a link between mitochondrial stress-induced GDF15 production and protection from tissue inflammation on aging in humans and mice.

The Role of Growth Differentiation Factor 15 in Energy Metabolism.

Growth differentiation factor 15 (GDF15) is receiving great interest beyond its role as an aging and disease-related biomarker. Recent discovery of its receptor, glial cell line-derived neurotrophic factor (GDNF) family receptor α-like (GFRAL), suggests a central role in appetite regulation. However, there is also considerable evidence that GDF15 may have peripheral activity through an as-of-yet undiscovered mode of action.

An adipocyte-specific defect in oxidative phosphorylation increases systemic energy expenditure and protects against diet-induced obesity in mouse models.

Aims/hypothesis: Mitochondrial oxidative phosphorylation (OxPhos) is essential for energy production and survival. However, the tissue-specific and systemic metabolic effects of OxPhos function in adipocytes remain incompletely understood.

Methods: We used adipocyte-specific Crif1 (also known as Gadd45gip1) knockout (AdKO) mice with decreased adipocyte OxPhos function.

Reduced oxidative capacity in macrophages results in systemic insulin resistance.

Oxidative functions of adipose tissue macrophages control the polarization of M1-like and M2-like phenotypes, but whether reduced macrophage oxidative function causes systemic insulin resistance in vivo is not clear. Here, we show that mice with reduced mitochondrial oxidative phosphorylation (OxPhos) due to myeloid-specific deletion of CR6-interacting factor 1 (Crif1), an essential mitoribosomal factor involved in biogenesis of OxPhos subunits, have M1-like polarization of macrophages and systemic insulin resistance with adipose inflammation. Macrophage GDF15 expression is reduced in mice with impaired oxidative function, but induced upon stimulation with rosiglitazone and IL-4.

Simultaneous cell disruption and lipid extraction of wet aurantiochytrium sp. KRS101 using a high shear mixer.

Microalgae are regarded as a promising source of biofuels, and the concept of a microalgae-based biorefinery has attracted increasing attention in recent years. From an economic perspective, however, the process remains far from competitive with fossil fuels. This is particularly true of lipid extraction, due in part to the energy-intensive drying step.

Growth Differentiation Factor 15 Mediates Systemic Glucose Regulatory Action of T-Helper Type 2 Cytokines.

T-helper type 2 (Th2) cytokines, including interleukin (IL)-13 and IL-4, produced in adipose tissue, are critical regulators of intra-adipose and systemic lipid and glucose metabolism. Furthermore, IL-13 is a potential therapy for insulin resistance in obese mouse models. Here, we examined mediators produced by adipocytes that are responsible for regulating systemic glucose homeostasis in response to Th2 cytokines.

ANGPTL6 expression is coupled with mitochondrial OXPHOS function to regulate adipose FGF21.

Recent studies revealed that the inhibition of mitochondrial oxidative phosphorylation (OXPHOS) is coupled with the mitochondrial unfolded protein response, thereby stimulating the secretion of non-cell autonomous factors, which may control systemic energy metabolism and longevity. However, the nature and roles of non-cell autonomous factors induced in adipose tissue in response to reduced OXPHOS function remain to be clarified in mammals. CR6-interacting factor 1 (CRIF1) is an essential mitoribosomal protein for the intramitochondrial production of mtDNA-encoded OXPHOS subunits.

Growth differentiation factor 15 is a myomitokine governing systemic energy homeostasis.

Reduced mitochondrial electron transport chain activity promotes longevity and improves energy homeostasis via cell-autonomous and -non-autonomous factors in multiple model systems. This mitohormetic effect is thought to involve the mitochondrial unfolded protein response (UPR), an adaptive stress-response pathway activated by mitochondrial proteotoxic stress. Using mice with skeletal muscle-specific deficiency of Crif1 (muscle-specific knockout [MKO]), an integral protein of the large mitoribosomal subunit (39S), we identified growth differentiation factor 15 (GDF15) as a UPR-associated cell-non-autonomous myomitokine that regulates systemic energy homeostasis.

Hypoxia-inducible factor-1α inhibition by a pyrrolopyrazine metabolite of oltipraz as a consequence of microRNAs 199a-5p and 20a induction.

Oltipraz, a cancer chemopreventive agent, has antitumor and antiangiogenic effects. In animal models and clinical studies, a considerable amount of oltipraz is metabolized to pyrrolopyrazines, including M2, 7-methyl-6,8-bis(methylthio)pyrrolo[1,2-a]pyrazine; M3, 7-methyl-8-(methylsulfinyl)-6-(methylthio)pyrrolo[1,2-a]pyrazine and M4, 7-methyl-6,8-bis(methylsulfinyl)pyrrolo[1,2-a]pyrazine. In view of the role of hypoxia-inducible factor-1 (HIF-1) α in tumor growth and angiogenesis, this study investigated whether pyrrolopyrazine metabolites of oltipraz inhibit HIF-1α induction, and if so, what the molecular basis is.