Gα12 ablation exacerbates liver steatosis and obesity by suppressing USP22/SIRT1-regulated mitochondrial respiration.

Nonalcoholic fatty liver disease (NAFLD) arises from mitochondrial dysfunction under sustained imbalance between energy intake and expenditure, but the underlying mechanisms controlling mitochondrial respiration have not been entirely understood. Heterotrimeric G proteins converge with activated GPCRs to modulate cell-signaling pathways to maintain metabolic homeostasis. Here, we investigated the regulatory role of G protein α12 (Gα12) on hepatic lipid metabolism and whole-body energy expenditure in mice.

A potent and selective 11β-hydroxysteroid dehydrogenase type 1 inhibitor, SKI2852, ameliorates metabolic syndrome in diabetic mice models.

11β-Hydroxysteroid dehydrogenase type 1 (11βHSD1) has been targeted for new drugs to treat type 2 diabetes and metabolic syndrome. In this study, we determined whether the inhibition of 11βHSD1 with a new selective inhibitor, SKI2852, could improve lipid profiles, glucose levels, and insulin sensitivity in type 2 diabetic and obese conditions. SKI2852 showed a potent inhibition of cortisone to cortisol conversion for over 80% in both liver and adipose tissue ex vivo from orally administered C57BL/6 mice, and in vivo analysis results were consistent with this.

Inverse agonist of nuclear receptor ERRγ mediates antidiabetic effect through inhibition of hepatic gluconeogenesis.

Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder with diverse pathological manifestations and is often associated with abnormal regulation of hepatic glucose production. Many nuclear receptors known to control the hepatic gluconeogenic program are potential targets for the treatment of T2DM and its complications. Nevertheless, the therapeutic potential of the estrogen-related receptor γ (ERRγ) in T2DM remains unknown.

A novel function of adipocytes in lipid antigen presentation to iNKT cells.

Systemic low-grade chronic inflammation has been intensively investigated in obese subjects. Recently, various immune cell types, such as macrophages, granulocytes, helper T cells, cytotoxic T cells, and B cells, have been implicated in the pathogenesis of adipose tissue inflammation. However, the roles of invariant natural killer T cells (iNKT cells) and the regulation of iNKT cell activity in adipose tissue are not thoroughly understood.

TCF7L2 modulates glucose homeostasis by regulating CREB- and FoxO1-dependent transcriptional pathway in the liver.

Peripheral insulin resistance contributes to the development of type 2 diabetes. TCF7L2 has been tightly associated with this disease, although the exact mechanism was largely elusive. Here we propose a novel role of TCF7L2 in hepatic glucose metabolism in mammals.

Role of hypothalamic proopiomelanocortin neuron autophagy in the control of appetite and leptin response.

Autophagy is a catabolic cellular process involving the degradation of the cell's own components. Although the role of autophagy of diverse tissues in body metabolism has been investigated, the importance of autophagy in hypothalamic proopiomelanocortin (POMC) neurons, key regulators of energy balance, has not been addressed. The role of autophagy in leptin sensitivity that is critical for the control of body weight and appetite has also not been investigated.

Hepatitis B virus X protein regulates hepatic glucose homeostasis via activation of inducible nitric oxide synthase.

Dysregulation of liver functions leads to insulin resistance causing type 2 diabetes mellitus and is often found in chronic liver diseases. However, the mechanisms of hepatic dysfunction leading to hepatic metabolic disorder are still poorly understood in chronic liver diseases. The current work investigated the role of hepatitis B virus X protein (HBx) in regulating glucose metabolism.

Endoplasmic reticulum stress promotes LIPIN2-dependent hepatic insulin resistance.

Objective: Diet-induced obesity (DIO) is linked to peripheral insulin resistance-a major predicament in type 2 diabetes. This study aims to identify the molecular mechanism by which DIO-triggered endoplasmic reticulum (ER) stress promotes hepatic insulin resistance in mouse models.

Research Design And Methods: C57BL/6 mice and primary hepatocytes were used to evaluate the role of LIPIN2 in ER stress-induced hepatic insulin resistance.

Suppressor of MEK null (SMEK)/protein phosphatase 4 catalytic subunit (PP4C) is a key regulator of hepatic gluconeogenesis.

Fasting promotes hepatic gluconeogenesis to maintain glucose homeostasis. The cAMP-response element binding protein (CREB)-regulated transcriptional coactivator 2 (CRTC2) is responsible for transcriptional activation of gluconeogenic genes and is critical for conveying the opposing hormonal signals of glucagon and insulin in the liver. Here, we show that suppressor of MEK null 1 (SMEK1) and SMEK2 [protein phosphatase 4 (PP4) regulatory subunits 3a and 3b, respectively] are directly involved in the regulation of hepatic glucose metabolism in mice.

Shear bond strength and failure types of polymethyl methacrylate denture base resin and titanium treated with surface conditioner.

This study compared the shear bond strength and failure types of a polymethyl methacrylate (PMMA) denture base resin to commercially pure (CP) titanium, Ti-6Al-4V alloy, and cobalt-chromium alloy using a metal surface conditioner. The PMMA denture base resin (5 x 5 x 5 mm(3)) was cured onto disks, 10 mm in diameter and 2.5-mm thick.

Regulation of hepatic gluconeogenesis by an ER-bound transcription factor, CREBH.

Endoplasmic reticulum (ER)-bound transcription factor families are shown to be involved in the control of various metabolic pathways. Here, we report a critical function of ER-bound transcription factor, CREBH, in the regulation of hepatic gluconeogenesis. Expression of CREBH is markedly induced by fasting or in the insulin-resistant state in rodents in a dexamethasone- and PGC-1alpha-dependent manner, which results in the accumulation of active nuclear form of CREBH (CREBH-N).

Effect of adhesive primers on bonding strength of heat cure denture base resin to cast titanium and cobalt-chromium alloy.

Statement Of Problem: The poor chemical bonding of a denture base resin to cast titanium framework often introduces adhesive failure and increases microleakage.

Purpose: This study evaluated the shear bond strengths of a heat cure denture base resin to commercially pure titanium, Ti-6Al-4V alloy and a cobalt-chromium alloy using two adhesive primers.

Material And Methods: Disks of commercially pure titanium, Ti-6Al-4V alloy and a cobalt-chromium alloy were cast.

Transient beta-glucuronidase expression in lily (Lilium longflorum L.) pollen via wounding-assisted Agrobacterium-mediated transformation.

A pollen-based transient expression system has been developed. Lily pollen grains, wounded by vigorous shaking in the presence of aluminum oxide particles, were transformed by infiltration with Agrobacterium tumefaciens LBA4404 cells harboring the beta-glucuronidase (GUS) gene construct, pBI121. In histochemical and fluorometric GUS analysis, the wounding processes allowed efficient transformation and, in cDNA blot hybridization, GUS mRNA synthesis was clearly detected.