The adiponectin-PPARγ axis in hepatic stellate cells regulates liver fibrosis.

Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear.

Adipogenin Dictates Adipose Tissue Expansion by Facilitating the Assembly of a Dodecameric Seipin Complex.

Adipogenin (Adig) is an evolutionarily conserved microprotein and is highly expressed in adipose tissues and testis. Here, we identify Adig as a critical regulator for lipid droplet formation in adipocytes. We determine that Adig interacts directly with seipin, leading to the formation of a rigid complex.

Downregulation of the kidney glucagon receptor, essential for renal function and systemic homeostasis, contributes to chronic kidney disease.

The glucagon receptor (GCGR) in the kidney is expressed in nephron tubules. In humans and animal models with chronic kidney disease, renal GCGR expression is reduced. However, the role of kidney GCGR in normal renal function and in disease development has not been addressed.

HSP47 levels determine the degree of body adiposity.

Adiposity varies among individuals with the influence of diverse physiological, pathological, environmental, hormonal, and genetic factors, but a unified molecular basis remains elusive. Here, we identify HSP47, a collagen-specific chaperone, as a key determinant of body adiposity. HSP47 expression is abundant in adipose tissue; increased with feeding, overeating, and obesity; decreased with fasting, exercise, calorie restriction, bariatric surgery, and cachexia; and correlated with fat mass, BMI, waist, and hip circumferences.

Endogenous renal adiponectin drives gluconeogenesis through enhancing pyruvate and fatty acid utilization.

Adiponectin is a secretory protein, primarily produced in adipocytes. However, low but detectable expression of adiponectin can be observed in cell types beyond adipocytes, particularly in kidney tubular cells, but its local renal role is unknown. We assessed the impact of renal adiponectin by utilizing male inducible kidney tubular cell-specific adiponectin overexpression or knockout mice.

Protective roles of adiponectin and molecular signatures of HNF4α and PPARα as downstream targets of adiponectin in pancreatic β cells.

The disease progression of the metabolic syndrome is associated with prolonged hyperlipidemia and insulin resistance, eventually giving rise to impaired insulin secretion, often concomitant with hypoadiponectinemia. As an adipose tissue derived hormone, adiponectin is beneficial for insulin secretion and β cell health and differentiation. However, the down-stream pathway of adiponectin in the pancreatic islets has not been studied extensively.

GPR92 activation in islet macrophages controls β cell function in a diet-induced obesity model.

The molecular mechanisms underlying obesity-induced increases in β cell mass and the resulting β cell dysfunction need to be elucidated further. Our study revealed that GPR92, expressed in islet macrophages, is modulated by dietary interventions in metabolic tissues. Therefore, we aimed to define the role of GPR92 in islet inflammation by using a high-fat diet-induced (HFD-induced) obese mouse model.

SARS-CoV-2 infection impairs the insulin/IGF signaling pathway in the lung, liver, adipose tissue, and pancreatic cells via IRF1.

Background: COVID-19 can cause multiple organ damages as well as metabolic abnormalities such as hyperglycemia, insulin resistance, and new onset of diabetes. The insulin/IGF signaling pathway plays an important role in regulating energy metabolism and cell survival, but little is known about the impact of SARS-CoV-2 infection. The aim of this work was to investigate whether SARS-CoV-2 infection impairs the insulin/IGF signaling pathway in the host cell/tissue, and if so, the potential mechanism and association with COVID-19 pathology.

Adiponectin preserves metabolic fitness during aging.

Adiponectin is essential for the regulation of tissue substrate utilization and systemic insulin sensitivity. Clinical studies have suggested a positive association of circulating adiponectin with healthspan and lifespan. However, the direct effects of adiponectin on promoting healthspan and lifespan remain unexplored.

From friend to foe: Pro-apoptotic action of nuclear ARC in diabetes.

Apoptosis repressor with caspase recruitment domain (ARC) is an established cytoplasmic anti-apoptotic factor relevant for cancer and metabolic disease. In this issue of Developmental Cell, McKimpson et al. show that ARC can assume potent pro-apoptotic effects in β cells of the endocrine pancreas via translocation to the nucleus.

A Novel Model of Diabetic Complications: Adipocyte Mitochondrial Dysfunction Triggers Massive β-Cell Hyperplasia.

Obesity-associated type 2 diabetes mellitus (T2DM) entails insulin resistance and loss of β-cell mass. Adipose tissue mitochondrial dysfunction is emerging as a key component in the etiology of T2DM. Identifying approaches to preserve mitochondrial function, adipose tissue integrity, and β-cell mass during obesity is a major challenge.

Dermal adipose tissue has high plasticity and undergoes reversible dedifferentiation in mice.

Dermal adipose tissue (also known as dermal white adipose tissue and herein referred to as dWAT) has been the focus of much discussion in recent years. However, dWAT remains poorly characterized. The fate of the mature dermal adipocytes and the origin of the rapidly reappearing dermal adipocytes at different stages remain unclear.

Lipotoxicity and Cell Maintenance in Obesity and Type 2 Diabetes.

Obesity and diabetes are often associated with lipotoxic conditions in multiple tissues. The insulin-producing cells are susceptible to elevated lipid levels and the ensuing lipotoxicity. The preservation of cell mass and function is one of the main goals of diabetes management under these metabolically stressful conditions.

β1 Syntrophin Supports Autophagy Initiation and Protects against Cerulein-Induced Acute Pancreatitis.

Syntrophins are a family of proteins forming membrane-anchored scaffolds and serving as adaptors for various transmembrane and intracellular signaling molecules. To understand the physiological roles of β1 syntrophin, one of the least characterized members, we generated mouse models to eliminate β1 syntrophin specifically in the endocrine or exocrine pancreas. β1 syntrophin is dispensable for the morphology and function of insulin-producing β cells.

Adipocyte GR Inhibits Healthy Adipose Expansion Through Multiple Mechanisms in Cushing Syndrome.

In Cushing syndrome, excessive glucocorticoids lead to metabolic disturbances, such as insulin resistance, adipocyte hypertrophy, and liver steatosis. In vitro experiments have highlighted the importance of adipocyte glucocorticoid receptor (GR), but its metabolic roles in vivo have not been fully elucidated in Cushing syndrome. In this study, using clinical samples from patients with Cushing syndrome and adipocyte-specific GR knockout (AGRKO) mice, we investigated the roles of adipocyte GR and its clinical relevance in Cushing syndrome.

Impact of MR on mature adipocytes in high-fat/high-sucrose diet-induced obesity.

Active glucocorticoid levels are elevated in the adipose tissue of obesity due to the enzyme 11 beta-hydroxysteroid dehydrogenase type 1. Glucocorticoids can bind and activate both glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), and pharmacological blockades of MR prevent high-fat diet-induced obesity and glucose intolerance. To determine the significance of MR in adipocytes, we generated adipocyte-specific MR-knockout mice (AdipoMR-KO) and fed them high-fat/high-sucrose diet.

SDF-1 Is an Autocrine Insulin-Desensitizing Factor in Adipocytes.

Insulin desensitization occurs not only under the obese diabetic condition but also in the fasting state. However, little is known about the common secretory factor(s) that are regulated under these two insulin-desensitized conditions. Here, using database analysis and in vitro and in vivo experiments, we identified stromal derived factor-1 (SDF-1) as an insulin-desensitizing factor in adipocytes, overexpressed in both fasting and obese adipose tissues.

Intracellular lipid metabolism impairs β cell compensation during diet-induced obesity.

The compensatory proliferation of insulin-producing β cells is critical to maintaining glucose homeostasis at the early stage of type 2 diabetes. Failure of β cells to proliferate results in hyperglycemia and insulin dependence in patients. To understand the effect of the interplay between β cell compensation and lipid metabolism upon obesity and peripheral insulin resistance, we eliminated LDL receptor-related protein 1 (LRP1), a pleiotropic mediator of cholesterol, insulin, energy metabolism, and other cellular processes, in β cells.

Eicosapentaenoic acid and 5-HEPE enhance macrophage-mediated Treg induction in mice.

Eicosapentaenoic acid (EPA) is an omega-3 fatty acid with immunomodulatory and anti-inflammatory effects. Beyond its direct effects, the metabolic products of EPA also regulate various immune responses. Animal experiments demonstrated that EPA reduces adipose inflammation in high fat diet-induced obese mouse.

Regulation of Dipeptidyl Peptidase-4, its Substrate Chemokines, and Their Receptors in Adipose Tissue of ob/ob Mice.

The physiological function of DPP-4 in proteolytic inactivation of incretins has been well established, however, there is limited information on the expression and the significance of DPP-4 in white adipose tissue with regard to obesity. The objective of the work was to reveal the expression and regulation of DPP-4 in adipocytes and compare the expression and activity of DPP-4 in white adipose tissue and several other organs such as the liver, muscle and kidney. We also investigated the gene expression levels of DPP-4 substrate chemokines, and their receptors in white adipose tissue.

Nur77 gene expression levels were involved in different ACTH-secretion autonomy between Cushing's disease and subclinical Cushing's disease.

Cushing's disease (CD) and subclinical Cushing's disease (subCD) are both diseases caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. However, ACTH autonomy in subCD is weaker than in CD and there are no Cushingoid features in subCD. The differences of molecular mechanisms in ACTH autonomy between CD and subCD have not yet been reported.

Adipose tissue macrophages induce PPARγ-high FOXP3(+) regulatory T cells.

Numerous regulatory T cells (Tregs) are present in adipose tissues compared with other lymphoid or non-lymphoid tissues. Adipose Tregs regulate inflammatory state and insulin sensitivity. However, the mechanism that maintains Tregs in adipose tissue remains unclear.

Clinical significance of fluctuations in thyroid hormones after surgery for Cushing's syndrome.

Patients with Cushing's syndrome (CS) frequently develop hyperthyroidism after surgery due to SITSH (syndrome of inappropriate secretion of TSH) and this SITSH contributed to the symptoms of steroid withdrawal syndrome (SWS). However, the duration of fluctuations in thyroid hormones after surgery for CS remains unknown. The aim of this prospective study was to investigate the clinical course of fluctuation in thyroid hormone level in CS patients after surgery.