Caloric restriction (CR) can reduce circulating leukocyte abundance and has been associated with changes in leukocyte compartmental distribution, but whether pharmacologic and dietary CR-related interventions induce comparable immune alterations under lean homeostatic conditions remains unclear. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly discussed as pharmacologic interventions that partially overlap with CR-related physiology, however, their steady-state immunological effects in lean organisms have not been well defined. Therefore, we compared semaglutide administration and intermittent fasting (IF) protocols in healthy lean mice, with particular attention to intervention regularity. Eight-week-old male C57BL/6 N mice were assigned to semaglutide or vehicle treatment and to IF regimens for 4 weeks. Semaglutide was administered either once daily or once every other day. Fasting interventions included alternate-day fasting (ADF) and irregular intermittent fasting (IIF). Major leukocyte subsets were quantified by flow cytometry in peripheral blood, bone marrow, and spleen. Body weight and serum corticosterone were also assessed. Group comparisons were performed using unpaired two-tailed Student’s t tests or one-way ANOVA with multiple comparison correction. Bone marrow myeloid progenitor proportions, immune-cell viability and Annexin V positivity, peripheral blood CXCR4 expression, and bone marrow supernatant CXCL12 concentrations were also assessed. Regular semaglutide administration was associated with reduced circulating leukocyte abundance and increased representation of selected leukocyte populations in the bone marrow, particularly natural killer cells and neutrophils, whereas non-standard dosing showed a distinct distribution pattern. IF was also associated with compartment-specific differences in leukocyte abundance. Compared with ADF, IIF showed a distinct pattern of circulating and bone marrow leukocyte abundance, although these findings should be interpreted as descriptive changes in compartmental distribution rather than direct evidence of altered trafficking. Semaglutide and fasting produced distinct patterns of leukocyte abundance across immune compartments in healthy lean mice. Accompanying changes in cell viability and CXCR4 expression identify survival and trafficking as potential contributors to these patterns and provide a basis for investigating how metabolic interventions regulate leukocyte distribution.
Irregular eating patterns, including day-to-day variability and meal timing differences, may be associated with metabolic risk. However, little is known about their associations with dietary and lifestyle insulin resistance indices (DIR and LIR). This study examined these associations among Iranian women. In this cross-sectional study, 626 participants aged 20–60 years completed three non-consecutive 24-hour dietary recalls. Day-to-day variability, expressed as the standard deviation, was calculated for total energy intake, energy intake after 4:00 and 6:00 p.m., and the number of eating occasions. Eating jetlag was calculated as the absolute difference in eating midpoint between workdays and free days, with eating midpoint defined as the midpoint between the first and last eating occasions. Anthropometric measurements and blood samples were collected. DIR showed moderate positive correlations with insulin (r = 0.36) and TG/HDL-C ratio (r = 0.34), while corresponding correlations for LIR were weaker (r = 0.19 and r = 0.21, respectively; P < 0.05). Greater variability in daily energy intake was associated with higher DIR [β = 81.74 (95
Cardio-renal–metabolic multimorbidity (CRMM), defined as the coexistence of at least two of cardiovascular disease, chronic kidney disease, and type 2 diabetes, is a growing public health concern. Dietary macronutrients play an important role in the management of diet-related chronic diseases. We aimed to investigate the association between macronutrient intake and CRMM risk, as well as the substitution of dietary macronutrients in relation to that risk. In this prospective cohort study, 2,539 adults (mean age 40.9 ± 13.5 years; BMI 27.1 ± 4.8 kg/m²) from the Tehran Lipid and Glucose Study were followed for a median of 11.6 years. Macronutrient intake was assessed using a validated 168-item food-frequency questionnaire. Cox models estimated hazard ratios (HRs) for CRMM across tertiles of macronutrient intake, as well as for macronutrient substitution in relation to CRMM risk, adjusting for demographic and lifestyle factors. During follow-up, 216 participants developed CRMM. Participants in the highest tertile of carbohydrate, fat and SFA intake had a higher risk of CRMM after adjustment for confounding factors (carbohydrate HR: 1.74, 95
The dietary index for gut microbiota (DI-GM) has been proposed based on studies to represent intestinal microbiome composition and is associated with cardiovascular disease (CVD) risk. A few cross-sectional studies from the National Health and Nutrition Examination Survey (NHANES) database have examined the association between DI-GM and the likelihood of CVD; however, there are no cohort studies from other communities. Therefore, this study examined the association between DI-GM and CVD risk using the Tehran Lipid and Glucose Study (TLGS) database. This cohort included 2,920 adults (≥ 19 years) without a history of CVD from TLGS (2006–2020). We calculated DI-GM using a food frequency questionnaire and ascertained incident CVD from participants’ medical records. We used the Cox proportional hazards model to assess the association between DI-GM and the risk of CVD. The mean age of participants was 39.3 years, and 55
Cardiovascular-kidney-metabolic (CKM) syndrome is a newly recognized multisystem disorder encompassing metabolic dysfunction, chronic kidney disease, and cardiovascular disease, with most individuals remaining in early stages (0–3). Chronic inflammation and abnormal adipose tissue distribution are central to CKM pathogenesis; however, the prognostic relevance of diet-related inflammatory exposure in combination with body shape–derived central adiposity during this early stage remains unclear. Data were derived from the National Health and Nutrition Examination Survey (NHANES) 2001–2018, including 32,976 adults with early-stage CKM syndrome. Dietary inflammatory potential was assessed using the Dietary Inflammatory Index (DII), calculated from dietary intake collected during the first 24-hour dietary recall in the primary analysis. In the sensitivity analysis restricted to participants from the 2003–2018 survey cycles with two valid 24-hour dietary recalls, the mean of the Day 1 and Day 2 recall-specific DII scores was used. Central adiposity was evaluated using A Body Shape Index (ABSI). All-cause mortality was the primary outcome, and cardiovascular disease (CVD) mortality was the secondary outcome. Multivariable Cox proportional hazards models were applied to examine independent and joint associations, with subgroup and sensitivity analyses conducted to assess robustness. During a mean follow-up of 102.5 months, 3,690 deaths occurred, including 1,004 due to CVD. Higher DII and ABSI were independently associated with increased all-cause mortality, while ABSI was also positively associated with CVD mortality. Notably, individuals with a dual high-risk profile—characterized by concomitantly high DII and high ABSI—exhibited the highest risks of both all-cause and CVD mortality. These associations appeared to be more pronounced among older adults, women, individuals with obesity, non-Hispanic White participants, and those with hypertension. In the repeated-recall sensitivity analysis, concomitantly high DII and high ABSI remained significantly associated with both all-cause and cardiovascular mortality, whereas high DII was significantly associated with cardiovascular mortality but not with all-cause mortality. This study provides novel population-based evidence that concomitantly high dietary inflammatory potential and central adiposity are associated with increased risks of both all-cause and cardiovascular mortality among adults with early-stage CKM syndrome, with these joint associations remaining statistically significant in the repeated-recall analysis. Although the DII-specific association with all-cause mortality was less consistent across dietary assessment approaches, the joint assessment of DII and ABSI may provide complementary information for mortality risk stratification in early-stage CKM syndrome.
