Obesity is a multifaceted condition linked to increased cardiometabolic disease risk, partly due to the endocrine function of adipose tissue and its secretion of adipokines, such as leptin and adiponectin. Leptin regulates food intake and energy expenditure and stimulates pro-inflammatory cytokines, while adiponectin exhibits anti-inflammatory, anti-atherogenic, and insulin-sensitizing properties. In obesity, adipose tissue remodeling leads to increased leptin and decreased adiponectin, disrupting metabolic homeostasis. The adiponectin:leptin (AL) ratio emerges as a biomarker for adipose tissue dysfunction, strongly correlating with inflammation, insulin resistance, and oxidative stress. This study aimed to explore the relationship between the AL ratio and cardiometabolic health in older adults with obesity and assess changes in the AL ratio following a 12-month exercise and diet intervention. The hypothesis was that the AL ratio would inversely correlate with adiposity and cardiometabolic biomarkers, and that a combined exercise, diet quality, and weight loss intervention would yield the greatest improvement in the AL ratio.

Existing research demonstrates a strong link between the AL ratio and adipose tissue dysfunction in adults, but studies on older adults are scarce. There's a lack of intervention research evaluating the AL ratio's sensitivity to lifestyle changes. Studies have shown that the AL ratio correlates more strongly with inflammation, insulin resistance, and oxidative stress than individual adipokine measures. Strategies to increase the AL ratio include weight loss, physical activity, and dietary modifications.

This ancillary study used data from the CROSSROADS randomized controlled trial (ClinicalTrial.gov #NCT00955903), involving 163 community-dwelling older adults (70.2 ± 4.7 years, 38% male) with obesity (BMI 30–40 kg/m²). Participants were randomized into three groups: exercise only, exercise + nutrient-dense weight maintenance, and exercise + nutrient-dense caloric restriction (500 kcal/d). All participants followed a standardized exercise program (90–150 min of moderate-vigorous cardiovascular exercise and two resistance training sessions weekly). Weight maintenance and weight loss groups received dietary counseling to improve quality, focusing on low-energy-dense foods. Cardiometabolic biomarkers (insulin, glucose, lipids, hsCRP, TNF-α, IL-6, adiponectin, leptin), adiposity measures (MRI, DXA), anthropometrics (BMI, waist circumference), and blood pressure were assessed at baseline and 12 months. The AL ratio was calculated as adiponectin (µg/mL)/leptin (ng/mL). Statistical analyses included Mann–Whitney U-tests, Spearman's correlations, and generalized linear mixed models (negative binomial distribution with log link function) to account for the skewed AL ratio distribution. The analysis controlled for biological sex.

At baseline, the AL ratio was significantly inversely correlated with BMI, waist circumference, adiposity measures, and insulin across all participants (p < 0.05). In females, significant correlations were also observed between the AL ratio and HDL-c, hsCRP, and IL-6. A significant time by intervention group interaction effect was found (p < 0.05). The AL ratio significantly increased from baseline to 12 months in the exercise + weight maintenance and exercise + intentional weight loss groups. Post-hoc analysis revealed a significantly greater AL ratio increase in the exercise + intentional weight loss group compared to other groups (p < 0.05). Improvements in the AL ratio correlated with changes in adiposity measures, particularly intra-abdominal adipose tissue.

The study supports the AL ratio as a measure of adipose tissue dysfunction in older adults. The inverse correlations between the AL ratio and adiposity and inflammatory markers align with previous research. The significant increase in the AL ratio following intervention, especially with intentional weight loss, highlights the impact of lifestyle interventions on improving adipose tissue function. The positive correlation between AL ratio and HDL-c suggests a potential beneficial role of HDL-c in adiponectin secretion. Differences in AL ratio between sexes highlight the need for sex-specific considerations in assessing adiposity and cardiometabolic health. The findings are consistent across diverse populations (Korean, Japanese, Hispanic, Slovenian), but this study is the first to investigate this in a biracial older adult population.

The AL ratio is a useful biomarker for adipose tissue dysfunction in older adults. A 12-month combined exercise and diet intervention, particularly with intentional weight loss, effectively improves the AL ratio. Future research should explore sex-specific responses and investigate the individual dietary components contributing to AL ratio changes.

This ancillary study was not powered to detect all potential relationships. The sample size may limit the generalizability of findings. Future studies with larger, more diverse populations are needed to confirm these results and explore the potential for sex-specific differences in response to interventions.