Renal sinus fat is associated with intrarenal hemodynamic abnormalities independent of visceral fat in patients with chronic kidney disease.

OBJECTIVE: Obesity is a risk factor of chronic kidney disease (CKD), contributing to the rising incidence of cardiometabolic diseases. Renal sinus fat (RSF) is an ectopic fat depot located at the renal cavity that could impair renal function and hemodynamic through compression of renal structures. The major purpose of this study was to explore the relationship between RSF accumulation and renal dysfunction in CKD patients. METHODS: We evaluated the associations between computed tomography measured RSF volume and key clinical and histologic parameters involved in renal function and hemodynamics in 132 well-characterized CKD patients who underwent renal biopsy (median age: 62 years; 63.6% men). RESULTS: RSF volume normalized by renal volume (RSF%) positively correlated with obesity-related traits such body mass index and visceral fat volume (VFV) (all P < 0.001) whereas it negatively correlated with estimated glomerular filtration rate (eGFR) (ρ = -0.42, P < 0.001) and 24-h urinary creatinine clearance (CCr) (ρ = -0.34, P < 0.001). Notably, we found robust positive correlations between RSF% and renal resistive index (RRI) measured by the Doppler ultrasound (ρ = 0.40, P < 0.001), and the histological severity of global glomerular sclerosis (ρ = 0.48, P < 0.001) and interstitial fibrosis and tubular atrophy (IFTA) (ρ = 0.35, P < 0.001). In the multivariate linear regression models, after accounting for potential confounders including VFV, RSF% remained significantly associated with CCr (ß = -0.26, P < 0.001), RRI (ß = 0.17, P = 0.022), global glomerular sclerosis (ß = 0.21, P = 0.002), and IFTA (ß = 0.17, P = 0.012). CONCLUSION: RSF accumulation is associated with renal dysfunction and hemodynamic abnormalities independent of visceral adiposity. Our results suggest that RSF may have a potential unique role in the pathogenesis of CKD.

Safety and efficacy of long-term nicotinamide mononucleotide supplementation on metabolism, sleep, and nicotinamide adenine dinucleotide biosynthesis in healthy, middle-aged Japanese men.

Obesity and aging are major risk factors for several life-threatening diseases. Accumulating evidence from both rodents and humans suggests that the levels of nicotinamide adenine dinucleotide (NAD+), a regulator of many biological processes, declines in multiple organs and tissues with aging and obesity. Administration of an NAD+ intermediate, nicotinamide mononucleotide (NMN), replenishes intracellular NAD+ levels and mitigates aging- and obesity-associated derangements in animal models. In this human clinical study, we aimed to investigate the safety and effects of 8-week oral administration of NMN on biochemical, metabolic, ophthalmologic, and sleep quality parameters as well as on chronological alterations in NAD+ content in peripheral tissues. An 8-week, single-center, single-arm, open-label clinical trial was conducted. Eleven healthy, middle-aged Japanese men received two 125-mg NMN capsules once daily before breakfast. The 8-week NMN supplementation regimen was well-tolerated; NAD+ levels in peripheral blood mononuclear cells increased over the course of NMN administration. In participants with insulin oversecretion after oral glucose loading, NMN modestly attenuated postprandial hyperinsulinemia, a risk factor for coronary artery disease (n = 3). In conclusion, NMN overall safely and effectively boosted NAD+ biosynthesis in healthy, middle-aged Japanese men, showing its potential for alleviating postprandial hyperinsulinemia.

Adipocyte NMNAT1 expression is essential for nuclear NAD+ biosynthesis but dispensable for regulating thermogenesis and whole-body energy metabolism.

Nicotinamide adenine dinucleotide (NAD+) functions as an essential cofactor regulating a variety of biological processes. The purpose of the present study was to determine the role of nuclear NAD+ biosynthesis, mediated by nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1), in thermogenesis and whole-body energy metabolism. We first evaluated the relationship between NMNAT1 expression and thermogenic activity in brown adipose tissue (BAT), a key organ for non-shivering thermogenesis. We found that reduced BAT NMNAT1expression was associated with inactivation of thermogenic gene program induced by obesity and thermoneutrality. Next, we generated and characterized adiponectin-Cre-driven adipocyte-specific Nmnat1 knockout (ANMT1KO) mice. Loss of NMNAT1 markedly reduced nuclear NAD+ concentration by approximately 70% in BAT. Nonetheless, adipocyte-specific Nmnat1 deletion had no impact on thermogenic (rectal temperature, BAT temperature and whole-body oxygen consumption) responses to ß-adrenergic ligand norepinephrine administration and acute cold exposure, adrenergic-mediated lipolytic activity, and metabolic responses to obesogenic high-fat diet feeding. In addition, loss of NMNAT1 did not affect nuclear lysine acetylation or thermogenic gene program in BAT. These results demonstrate that adipocyte NMNAT1 expression is required for maintaining nuclear NAD+ concentration, but not for regulating BAT thermogenesis or whole-body energy homeostasis.

Interactions between Intestinal Homeostasis and NAD+ Biology in Regulating Incretin Production and Postprandial Glucose Metabolism.

The intestine has garnered attention as a target organ for developing new therapies for impaired glucose tolerance. The intestine, which produces incretin hormones, is the central regulator of glucose metabolism. Glucagon-like peptide-1 (GLP-1) production, which determines postprandial glucose levels, is regulated by intestinal homeostasis. Nicotinamide phosphoribosyltransferase (NAMPT)-mediated nicotinamide adenine dinucleotide (NAD+) biosynthesis in major metabolic organs such as the liver, adipose tissue, and skeletal muscle plays a crucial role in obesity- and aging-associated organ derangements. Furthermore, NAMPT-mediated NAD+ biosynthesis in the intestines and its upstream and downstream mediators, adenosine monophosphate-activated protein kinase (AMPK) and NAD+-dependent deacetylase sirtuins (SIRTs), respectively, are critical for intestinal homeostasis, including gut microbiota composition and bile acid metabolism, and GLP-1 production. Thus, boosting the intestinal AMPK-NAMPT-NAD+-SIRT pathway to improve intestinal homeostasis, GLP-1 production, and postprandial glucose metabolism has gained significant attention as a novel strategy to improve impaired glucose tolerance. Herein, we aimed to review in detail the regulatory mechanisms and importance of intestinal NAMPT-mediated NAD+ biosynthesis in regulating intestinal homeostasis and GLP-1 secretion in obesity and aging. Furthermore, dietary and molecular factors regulating intestinal NAMPT-mediated NAD+ biosynthesis were critically explored to facilitate the development of new therapeutic strategies for postprandial glucose dysregulation.

Intestinal Epithelial NAD+ Biosynthesis Regulates GLP-1 Production and Postprandial Glucose Metabolism in Mice.

Obesity is associated with perturbations in incretin production and whole-body glucose metabolism, but the precise underlying mechanism remains unclear. Here, we tested the hypothesis that nicotinamide phosphoribosyltransferase (NAMPT), which mediates the biosynthesis of nicotinamide adenine dinucleotide (NAD+), a key regulator of cellular energy metabolism, plays a critical role in obesity-associated intestinal pathophysiology and systemic metabolic complications. To this end, we generated a novel mouse model, namely intestinal epithelial cell-specific Nampt knockout (INKO) mice. INKO mice displayed diminished glucagon-like peptide-1 (GLP-1) production, at least partly contributing to reduced early-phase insulin secretion and postprandial hyperglycemia. Mechanistically, loss of NAMPT attenuated the Wnt signaling pathway, resulting in insufficient GLP-1 production. We also found that diet-induced obese mice had compromised intestinal NAMPT-mediated NAD+ biosynthesis and Wnt signaling pathway, associated with impaired GLP-1 production and whole-body glucose metabolism, resembling the INKO mice. Finally, administration of a key NAD+ intermediate, nicotinamide mononucleotide (NMN), restored intestinal NAD+ levels and obesity-associated metabolic derangements, manifested by a decrease in ileal Proglucagon expression and GLP-1 production as well as postprandial hyperglycemia in INKO and diet-induced obese mice. Collectively, our study provides mechanistic and therapeutic insights into intestinal NAD+ biology related to obesity-associated dysregulation of GLP-1 production and postprandial hyperglycemia.

A Case of New-Onset Systemic Lupus Erythematosus With Serositis in a Maintenance Hemodialysis Patient.

A 61-year-old woman with a 4-year history of maintenance hemodialysis due to end-stage renal disease of unknown cause was admitted because of a recurrent fever and abdominal pain lasting for 3 months. She had rheumatoid arthritis as a complication and had taken sulfasalazine for over 4 years. Laboratory data revealed thrombocytopenia, hypocomplementemia, a high C-reactive protein level, and positivity for antinuclear antibody and anti-double strand DNA antibody. Gallium scintigraphy showed pericarditis, pleuritis, and peritonitis. Nonscarring alopecia was also noted. She was diagnosed as having systemic lupus erythematosus (SLE). Drug-induced lupus elicited by sulfasalazine was ruled out because the symptoms did not improve even after the discontinuation of the drug upon admission. Oral prednisolone treatment markedly improved her symptoms and laboratory data. However, she later died of sepsis arising from proctitis on day 71 of admission. This report underscores the necessity of considering new-onset SLE in patients with unexplained fever and serositis, including pleuritis, peritonitis, or pericarditis, even if they are receiving maintenance dialysis.

Association of social skills with psychological distress among female nurses in Japan.

Nursing is a highly stressful occupation. Because nursing work involves interaction with patients and colleagues, competence in social skills may be a key issue in stress management among nurses. However, there are very few studies among nurses focused on social skills together with social support, both of which are important aspects of job stress. The aim of this study was to examine the interrelationships between social skills and social support with job stressors, problem-solving coping, and psychological distress among Japanese nurses. Data from a self-administered questionnaire of 1,197 female nurses who worked for 5 general hospitals in Japan were analyzed. Covariance structure analysis with structural equation modeling techniques showed that social skills and social support were positively related to each other, while they were negatively associated with psychological distress and job stressors, and positively associated with problem-solving coping. Furthermore, the direct association between social skills and psychological distress was stronger than the association between social support and psychological distress. These findings suggested that improving not only social support at work but also individual social skills is important for nurses' mental health.

[Longitudinal study of the situational specificity of coping strategies].

This longitudinal study examines the situational specificity of coping strategies for 3 943 male employees of the research and development division of an industrial company. The Job Stress Scale-Revised version (JSS-R) was administered twice to the same subjects 40 months apart to assess chronic job stressors (qualitative and quantitative) and coping strategies (problem-solving, support-seeking, and problem-leaving). Analysis of variance (ANOVA) was used to examine changes in coping strategies corresponding to changes in chronic job stressors. The results suggest a situational specificity of coping strategies. (a) With decreasing qualitative stressors, "problem-solving" coping increases and "problem-leaving" coping decreases. (b) With increasing qualitative stressors, "problem-leaving" coping increases and "problem-solving" coping decreases. (c) With increasing quantitative stressors, "support-seeking" coping increases. (d) With decreasing quantitative stressors, "problem-leaving" coping decreases. (e) There is no variance in "problem-leaving" coping attributable to the change in the quantitative stressors when the qualitative stressors decrease or increase. "Problem-leaving" coping is more strongly related to qualitative than quantitative stressors.

The impact of health problems on depression and activities in middle-aged and older adults: age and social interactions as moderators.

In this study, we compared the impact of health problems (HPs) on everyday activities and depressive symptoms between middle-aged and older adults. We also examined what type and source of social interactions moderate the noxious effects of HPs. Longitudinal analyses of data with 1,802 Japanese community-dwelling adults indicated that HPs were significantly related to (a) an increase in depressive symptoms among middle-aged adults and (b) a decline in everyday activities among older adults. The former was buffered by emotional family support, whereas the latter (b) was buffered by instrumental family support and, surprisingly, by negative interactions with family. In contrast, social interactions with other friends and acquaintances did not show any moderating effect.

[Construction of a stress reaction scale based on an item response model and examination of the developmental process of psychological stress reactions by using test characteristic curves].

In this study, a stress reaction scale was constructed based on an Item Response Model, and the developmental process of psychological stress reactions was investigated by using test characteristic curves. Subjects consisted of 286 private college students and 234 national college students. The Job Stress Scale (JSS) was revised for college students, and used to assess psychological stress reaction. Graded response model of Item Response Theory (IRT) was used to estimate parameters. After estimating item and subject parameters, we assessed the precision of measurement and the fit of the model, and found both precision and fit to be satisfactory. Then we examined the test characteristic curves of each subscale to investigate the developmental process of psychological stress reactions of college students in comparison with company employees.

[Effects of shift work schedule on mood changes among female nurses].

This study examined the short-term effects of shift work on mood changes. The subjects were 1,608 Japanese female nurses, working on rotating 3-shift schedules consisted of day, evening, and night shift. Repeated measurements of six dimensions of mood and sleep hours in four consecutive days were analyzed. Prominent changes of subjective fatigue, activity and confusion were observed especially when shift changes occurred (e.g., day shift to night shift or night shift to evening shift). The changes of mood were contingent to those of sleep hours, which suggested the close association between them. However, the mood changes were observed even after adjusting for the effect of sleep hours, indicating that irregular sleep pattern is not the only cause that affects mood.