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ABSTRACT Background and Aims Hypertensive emergencies, characterized by elevated blood pressure (BP) and multiple organ damage, have poor prognosis. Patients occasionally show gradual improvement in renal function with appropriate antihypertensive treatment despite renal impairment. However, reports analyzing factors predicting prognosis in patients with hypertensive emergencies and severe renal impairment are limited. This retrospective study aimed to investigate clinical features and predictors of renal outcomes in such patients. Methods Patients admitted to our hospital diagnosed with hypertensive emergency with severe renal impairment (serum creatinine [Cr] level > 2.5 mg/dL) between 2007 and 2021, were enrolled and divided into two groups: those who received renal replacement therapy (RRT) after 3 years (RRT group) and those who did not (non‐RRT group); clinical characteristics and laboratory data were compared. Results Fifteen patients were enrolled, with a median age and serum Cr level of 48 years and 5.97 mg/dL, respectively. No significant between‐group difference was observed in serum Cr levels or kidney size. However, the non‐RRT group exhibited significantly higher levels of serum lactate dehydrogenase (LDH) levels and significantly lower platelet counts (PLT), suggesting development of microangiopathic hemolysis due to severe endothelial damage. Furthermore, the non‐RRT group exhibited lower serum potassium levels than the RRT group, accompanied by high plasma renin activity and serum aldosterone levels, suggesting activation of the renin‐angiotensin system (RAS). In the non‐RRT group, serum Cr, LDH, potassium levels, and PLT improved significantly after treatment. Conclusions Serum LDH, potassium levels, and PLT are useful predictors of renal prognosis in hypertensive emergencies with extremely poor renal function. In some cases, severe renal damage can be ameliorated by appropriate antihypertensive therapy. A positive response to treatment often signifies a favorable prognosis. Furthermore, early initiation of RAS inhibitors may be beneficial for lowering BP and providing renal protection.

Abstract Obesity is among the risk factors for male infertility. Although several mechanisms underlying obesity-induced male subfertility have been reported, the entire mechanism of obesity-induced male infertility still remains unclear. Here, we show that sperm count, sperm motility and sperm fertilizing ability were decreased in male mice fed a high-fat diet and that the expression of the AdipoR1 gene and protein was decreased, and the expression of pro-apoptotic genes and protein increased, in the testis from mice fed a high-fat diet. Moreover, we demonstrate that testes weight, sperm count, sperm motility and sperm fertilizing ability were significantly decreased in AdipoR1 knockout mice compared to those in wild-type mice; furthermore, the phosphorylation of AMPK was decreased, and the expression of pro-apoptotic genes and proteins, caspase-6 activity and pathologically apoptotic seminiferous tubules were increased, in the testis from AdipoR1 knockout mice. Furthermore, study findings show that orally administrated AdipoRon decreased caspase-6 activity and apoptotic seminiferous tubules in the testis, thus ameliorating sperm motility in male mice fed a high-fat diet. This was the first study to demonstrate that decreased AdipoR1/AMPK signaling led to increased caspase-6 activity/increased apoptosis in the testis thus likely accounting for male infertility.

Abstract Background and Aim This study aimed to clarify the efficacy and safety of 48‐week pemafibrate treatment in patients with metabolic dysfunction‐associated steatotic liver disease (MASLD) complicated by dyslipidemia. Methods A total of 110 patients diagnosed with MASLD complicated by dyslipidemia received pemafibrate at a dose of 0.1 mg twice daily for 48 weeks. Results The participants were 54 males and 37 females, with a median age of 63 (52–71) years. Besides improvement in lipid profile, significant reductions from baseline to 48 weeks of treatment were found in liver‐related enzymes, such as aspartate aminotransferase, alanine aminotransferase (ALT), gamma‐glutamyl transpeptidase, and alkaline phosphatase (P

Abstract Alopecia induced by aging or side effects of medications affects millions of people worldwide and impairs the quality of life; however, there is a limit to the current medications. Here, we identify a small transdermally deliverable 5‐mer peptide (GLYYF; P5) that activates adiponectin receptor 1 (AdipoR1) and promotes hair growth. P5 sufficiently reproduces the biological effect of adiponectin protein via AMPK signaling pathway, increasing the expression of hair growth factors in the dermal papilla cells of human hair follicle. P5 accelerates hair growth ex vivo and induces anagen hair cycle in mice in vivo. Furthermore, we elucidate a key spot for the binding between AdipoR1 and adiponectin protein using docking simulation and mutagenesis studies. This study suggests that P5 could be used as a topical peptide drug for alleviating pathological conditions, which can be improved by adiponectin protein, such as alopecia.

Abstract Aims/Introduction The prevalence of obesity is rising in Japan and represents a considerable unmet medical need. The Awareness, Care and Treatment in Obesity MaNagement – International Observation (ACTION‐IO) study was designed to identify the perceptions, attitudes and barriers to obesity care among people with obesity (PwO) and healthcare professionals (HCPs) in Japan. Materials and Methods An online, cross‐sectional survey was carried out in 11 countries, including Japan. Results The survey was completed by 2,001 PwO and 302 HCPs in Japan. Fewer PwO (58%) than HCPs (85%) perceived obesity as a chronic disease. Most PwO (81%) thought that weight loss was their own responsibility, and waited a considerable time before seeking support from their HCP (mean 6 years). Most PwO (64%) had made one or more serious weight loss attempt in the past. In contrast, a serious attempt at losing weight was reported by HCPs for just 21% of their patients. Just 24% of PwO had weight discussions with an HCP in the past 5 years; of those, 56% expressed positive feelings after such a conversation, and just 2% felt offended. Lack of patient motivation (68%) and patient disinterest (61%) were reported by HCPs as barriers to weight management conversations. A higher proportion of obesity specialists (37%) than non‐specialists (22%) thought their patients were motivated to lose weight. Conclusions Our Japanese dataset shows a need to raise awareness of the pathophysiological basis and clinical management of obesity among PwO and HCPs. The largely positive feelings expressed by PwO after weight loss conversations should encourage HCPs to initiate earlier discussions before obesity‐related complications occur.

Masato Iwabu and Miki Okada-Iwabu et al. investigate whether diabetic phenotypes associated with disruption of the adiponectin receptor (AdipoR1) can be reversed in diabetic mice by upregulation of the receptor. They show that overexpressing human AdipoR1 in the muscles of diabetic mice increased insulin sensitivity and exercise endurance, suggesting a possible route for future clinical therapies.

Since December 2019, coronavirus disease 2019 (COVID-19) caused by a novel coronavirus has spread all over the world affecting tens of millions of people. Another pandemic affecting the modern world, type 2 diabetes mellitus is among the major risk factors for mortality from COVID-19. Current evidence, while limited, suggests that proper blood glucose control may help prevent exacerbation of COVID-19 even in patients with type 2 diabetes mellitus. Under current circumstances where the magic bullet for the disease remains unavailable, it appears that the role of blood glucose control cannot be stressed too much. In this review the profile of each anti-diabetic agent is discussed in relation to COVID-19.

The number of patients with obesity continues to increase seriously worldwide. It has become clear that, against a background of insulin resistance, obesity induces the so-called metabolic syndrome consisting of diabetes, hypertension, and dyslipidemia, leading, consequently, to an increased incidence of cardiovascular disease in affected individuals. It is shown that environmental factors, e.g., high-fat diet and lack of physical activity, not only promote the onset of obesity but lead to impairment of the action of adiponectin and its receptors, thus accounting in part for the onset of insulin resistance, type 2 diabetes/metabolic syndrome, and atherosclerosis in modern society. This review is intended to highlight some milestones in adipocyte research from the discovery of the insulin-sensitizing properties of adiponectin to the elucidation of the structures of its receptors, as well as to clarify their therapeutic implications and prospects for lifestyle-related diseases.

Obesity associated with unhealthy diet and lack of exercise is shown to contribute to the onset and/or aggravation of the metabolic syndrome and diabetes, thus placing affected individuals at increased risk of cardiovascular disease and cancer. Plasma adiponectin levels are decreased in obesity, which causes insulin resistance and diabetes. Therefore, we identified adiponectin receptors (AdipoRs) as the therapeutic target. It was suggested that, similarly to caloric restriction and exercise, activation of the AdipoRs may have the potential not only to improve lifestyle-related diseases but to contribute to prolonged the shortened lifespan on a high caloric unhealthy diet. To this end, we have identified "AdipoRon" as an adiponectin receptor agonist. Indeed, AdipoRon ameliorated diabetes associated with obesity as well as to increase exercise endurance, thus prolonging shortened lifespan of obese mice fed on a high fat diet. Additionally, we have recently determined the crystal structures of the human AdipoRs. The seven-transmembrane helices of AdipoRs are structurally distinct from those of G-protein coupled receptors. It is expected that these findings will contribute not only to the elucidation of the AdipoR-related signal transduction but to the development and optimization of AdipoR-targeted therapeutics for obesity-related diseases such as diabetes.

Identification of regulatory elements within the genome is crucial for understanding the mechanisms that govern cell type-specific gene expression. We generated genome-wide maps of open chromatin sites in 3T3-L1 adipocytes (on day 0 and day 8 of differentiation) and NIH-3T3 fibroblasts using formaldehyde-assisted isolation of regulatory elements coupled with high-throughput sequencing (FAIRE-seq). FAIRE peaks at the promoter were associated with active transcription and histone modifications of H3K4me3 and H3K27ac. Non-promoter FAIRE peaks were characterized by H3K4me1+/me3-, the signature of enhancers, and were largely located in distal regions. The non-promoter FAIRE peaks showed dynamic change during differentiation, while the promoter FAIRE peaks were relatively constant. Functionally, the adipocyte- and preadipocyte-specific non-promoter FAIRE peaks were, respectively, associated with genes up-regulated and down-regulated by differentiation. Genes highly up-regulated during differentiation were associated with multiple clustered adipocyte-specific FAIRE peaks. Among the adipocyte-specific FAIRE peaks, 45.3% and 11.7% overlapped binding sites for, respectively, PPARγ and C/EBPα, the master regulators of adipocyte differentiation. Computational motif analyses of the adipocyte-specific FAIRE peaks revealed enrichment of a binding motif for nuclear family I (NFI) transcription factors. Indeed, ChIP assay showed that NFI occupy the adipocyte-specific FAIRE peaks and/or the PPARγ binding sites near PPARγ, C/EBPα, and aP2 genes. Overexpression of NFIA in 3T3-L1 cells resulted in robust induction of these genes and lipid droplet formation without differentiation stimulus. Overexpression of dominant-negative NFIA or siRNA-mediated knockdown of NFIA or NFIB significantly suppressed both induction of genes and lipid accumulation during differentiation, suggesting a physiological function of these factors in the adipogenic program. Together, our study demonstrates the utility of FAIRE-seq in providing a global view of cell type-specific regulatory elements in the genome and in identifying transcriptional regulators of adipocyte differentiation.