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Background: Several modifiable risk factors, including dietary habits, are linked to cardiovascular disease (CVD) progression. However, lifestyle changes remain notoriously challenging, perhaps due to psychosocial factors. This pilot study aims to investigate the relationship between adherence to a healthy diet, CVD risk factors, psychological factors and sociodemographic variables among middle-aged adults in Sweden., Methods: Data were collected from March to December 2012 in the SCAPIS diet sub-study, where a total of 200 participants aged 50-64 years were enrolled. Dietary intake was assessed using the MiniMeal-Q food frequency questionnaire, and adherence to healthy eating patterns was evaluated using the Diet Quality Index-Swedish Nutrition Recommendations (DQI-SNR). Psychological factors, stress and sleep patterns were assessed through a comprehensive questionnaire. Statistical analyses included t-tests, analysis of variance, X 2 tests and logistic regression to identify predictors of unfavourable apolipoprotein (Apo) B/Apo A1 ratios., Results: Out of 200 participants, 182 had complete and reliable dietary data. The majority exhibited intermediate adherence to a healthy diet, with women showing better adherence to dietary fibre intake compared with men. Women with high dietary quality had better cardiovascular profiles, including higher levels of Apo A1 and high-density lipoprotein cholesterol, lower Apo B/Apo A1 ratios and higher plasma carotenoids. Significant predictors of unfavourable Apo B/Apo A1 ratios included low socioeconomic status (SES), higher body mass index, larger waist circumference and smoking. Stratified adjusted analyses revealed distinct predictors based on SES, with depression increasing the OR of an unfavourable lipid profile by 6.41 times (p=0.019) in low SES areas., Conclusions: This study highlights the potential of tailored recommendations considering socioeconomic and psychological factors. Addressing mental health and promoting physical activity may be crucial for CVD risk reduction, particularly in low SES areas. Further research is needed to confirm these findings in larger cohorts and to develop targeted interventions for diverse population groups., Competing Interests: None declared., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Dysregulated branched-chain amino acid (BCAA) metabolism has emerged as a key metabolic feature associated with the obese insulin-resistant state, and adipose BCAA catabolism is decreased in this context. BCAA catabolism is upregulated early in adipogenesis, but the impact of suppressing this pathway on the broader metabolic functions of the resultant adipocyte remains unclear. Here, we use CRISPR/Cas9 to decrease BCKDHA in 3T3-L1 and human pre-adipocytes, and ACAD8 in 3T3-L1 pre-adipocytes to induce a deficiency in BCAA catabolism through differentiation. We characterize the transcriptional and metabolic phenotype of 3T1-L1 cells using RNAseq and 13 C metabolic flux analysis within a network spanning glycolysis, tricarboxylic acid (TCA) metabolism, BCAA catabolism, and fatty acid synthesis. While lipid droplet accumulation is maintained in Bckdha-deficient adipocytes, they display a more fibroblast-like transcriptional signature. In contrast, Acad8 deficiency minimally impacts gene expression. Decreased glycolytic flux emerges as the most distinct metabolic feature of 3T3-L1 Bckdha-deficient cells, accompanied by a ∼40% decrease in lactate secretion, yet pyruvate oxidation and utilization for de novo lipogenesis is increased to compensate for the loss of BCAA carbon. Deletion of BCKDHA in human adipocyte progenitors also led to a decrease in glucose uptake and lactate secretion; however, these cells did not upregulate pyruvate utilization, and lipid droplet accumulation and expression of adipocyte differentiation markers was decreased in BCKDH knockout cells. Overall our data suggest that human adipocyte differentiation may be more sensitive to the impact of decreased BCKDH activity than 3T3-L1 cells and that both metabolic and regulatory cross-talk exist between BCAA catabolism and glycolysis in adipocytes. Suppression of BCAA catabolism associated with metabolic syndrome may result in a metabolically compromised adipocyte., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Objectives: Napping is a common habit in many countries. Nevertheless, studies about the chronic effects of napping on obesity are contradictory, and the molecular link between napping and metabolic alterations has yet to be studied. We aim to identify molecular mechanisms in adipose tissue (AT) that may connect napping and abdominal obesity., Methods: In this cross-sectional study, we extracted the RNA repeatedly across 24 hours from cultured AT explants and performed RNA sequencing. Circadian rhythms were analyzed using six consecutive time points across 24 hours. We also assessed global gene expression in each group (nappers vs. non-nappers)., Results: With napping, there was an 88% decrease in the number of rhythmic genes compared to that in non-nappers, a reduction in rhythm amplitudes of 29%, and significant phase changes from a coherent unimodal acrophase in non-nappers, towards a scattered and bimodal acrophase in nappers. Those genes that lost rhythmicity with napping were mainly involved in pathways of glucose and lipid metabolism, and of the circadian clock. Additionally, we found differential global gene expression between nappers and non-nappers with 34 genes down- and 32 genes upregulated in nappers. The top upregulated gene (IER3) and top down-regulated pseudogene (VDAC2P2) in nappers have been previously shown to be involved in inflammation., Conclusions: These new findings have implications for our understanding of napping's relationship with obesity and metabolic disorders., (Published by Oxford University Press on behalf of Sleep Research Society (SRS) 2024.)

Background and Purpose: Napping is a widespread practice worldwide and has in recent years been linked to increased abdominal adiposity. Lipase E or LIPE encodes the protein hormone-sensitive lipase (HSL), an enzyme that plays an important role in lipid mobilization and exhibits a circadian expression rhythm in human adipose tissue. We hypothesized that habitual napping may impact the circadian expression pattern of LIPE , which in turn may attenuate lipid mobilization and induce abdominal fat accumulation., Methods: Abdominal adipose tissue explants from participants with obesity (n = 17) were cultured for a 24-h duration and analyzed every 4 h. Habitual nappers (n = 8) were selected to match non-nappers (n = 9) in age, sex, BMI, adiposity, and metabolic syndrome traits. Circadian LIPE expression rhythmicity was analyzed using the cosinor method., Results: Adipose tissue explants exhibited robust circadian rhythms in LIPE expression in non-nappers. In contrast, nappers had a flattened rhythm. LIPE amplitude was decreased in nappers as compared with non-nappers (71% lower). The decrease in amplitude among nappers was related to the frequency of napping (times per week) where a lower rhythm amplitude was associated with a higher napping frequency (r = -0.80; P = 0.018). Confirmatory analyses in the activity of LIPE 's protein (i.e., HSL) also showed a significant rhythm in non-nappers, whereas significance in the activity of HSL was lost among nappers., Conclusion: Our results suggest that nappers display dysregulated circadian LIPE expression as well as dysregulated circadian HSL activity, which may alter lipid mobilization and contribute to increased abdominal obesity in habitual nappers., Competing Interests: FS served on the Board of Directors for the Sleep Research Society and has received consulting fees from the University of Alabama at Birmingham and Morehouse School of Medicine. FS’ interests were reviewed and managed by Brigham and Women’s Hospital and Partners HealthCare in accordance with their conflict-of-interest policies. FS’ consultancies are not related to the current work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zambrano, Kulyté, Luján, Rivero-Gutierrez, Sánchez de Medina, Martínez-Augustin, Ryden, Scheer and Garaulet.)

Mitochondrial dysfunction is a characteristic trait of human and rodent obesity, insulin resistance, and fatty liver disease. Here we report that mitochondria undergo fragmentation and reduced oxidative capacity specifically in inguinal white adipose tissue after feeding mice high fat diet (HFD) by a process dependent on the small GTPase RalA. RalA expression and activity are increased in white adipocytes from mice fed HFD. Targeted deletion of Rala in white adipocytes prevents the obesity-induced fragmentation of mitochondria and produces mice resistant to HFD-induced weight gain via increased fatty acid oxidation. As a result, these mice also exhibit improved glucose tolerance and liver function. In vitro mechanistic studies revealed that RalA suppresses mitochondrial oxidative function in adipocytes by increasing fission through reversing the protein kinase A-catalyzed inhibitory Ser 637 phosphorylation of the mitochondrial fission protein Drp1. Active RalA recruits protein phosphatase 2A (PP2Aa) to specifically dephosphorylate this inhibitory site on Drp1, activating the protein, thus increasing mitochondrial fission. Adipose tissue expression of the human homolog of Drp1, DNML1, is positively correlated with obesity and insulin resistance in patients. Thus, chronic activation of RalA plays a key role in repressing energy expenditure in obese adipose tissue by shifting the balance of mitochondrial dynamics towards excessive fission, contributing to weight gain and related metabolic dysfunction., Competing Interests: Competing interests The authors declare no competing interests.