Background: Adiponectin is an adipokine with insulin-sensitizing, anti-inflammatory, and cytoprotective properties that also plays a key role in metabolic adaptation to exercise. Although its regulation after resistance exercise has been extensively documented, less is known about its short-term modulation and its correlation with muscle damage markers following resistance training. Methods: Nine resistance-trained young men completed two sessions of total-body resistance exercise: (1) high time under tension (TUT) (5-1-2-1 cadence, to failure; ETS1) and (2) moderate TUT (2-1-2-1 cadence, two repetitions in reserve; ETS2). Plasma and saliva samples were collected before exercise and at 15 min, 24 h, and 48 h after exercise to assess total adiponectin by ELISA. Plasma creatine kinase (CK) and a Visual Analog Scale (VAS) were also measured for muscle soreness. Results: Plasma adiponectin significantly decreased from baseline to 48 h post-exercise in both sessions (p < 0.001), with no differences between the TUT conditions. Salivary adiponectin remained unchanged. Although a significant increase in CK and a decrease in adiponectin were observed at the group level, correlation analysis revealed no significant linear relationship between the magnitude of CK elevation and adiponectin reduction. Conclusions: Overall, these findings support the role of adiponectin as a marker of acute metabolic adaptation to resistance exercise. Acute resistance exercise elicited a time-dependent decrease in circulating adiponectin, irrespective of TUT. The temporal pattern of adiponectin decrease coincided with the rise in muscle damage markers, yet the lack of direct correlation suggests distinct regulatory mechanisms, while the lack of salivary changes underscores the complexity of adipokine regulation in vivo and suggests that saliva is not a reliable indicator of changes in circulating adiponectin.

Background: Colorectal cancer (CRC) remains one of the most prevalent and lethal malignancies worldwide. Adiponectin, a hormone secreted by adipose tissue, has been increasingly recognized for its pleiotropic effects in several malignancies. In particular, an inverse association between circulating adiponectin levels and CRC incidence supports a potential protective role for adiponectin and its receptors (AdipoR1, AdipoR2). The aim of this study was to investigate the effects of adiponectin on Caco-2 cells, a human CRC cell line, by examining intestinal epithelial differentiation using AdipoRon (AR), a synthetic adiponectin receptor agonist. Methods: The effects of AR on Caco-2 cells were assessed by evaluating dome formation and the expression of key molecular markers involved in intestinal epithelial differentiation, including KLF-4, DPPIV, SI, and KRT20, at both transcriptional levels using qRT-PCR and at protein levels using immunofluorescence and Western blot analysis. In addition, mitochondrial reactive oxygen species (ROS) production was assessed using MitoSOX™ Red. Results: Our findings showed that AR administration was associated with a dose-dependent increase in AdipoR1 and AdipoR2 expression as well as with dome formation in Caco-2 cells. Furthermore, AR administration reduced Ki-67 expression with no changes in cell cycle and an increase in the differentiation markers DPPIV and SI, while KRT20 remained unchanged. Finally, AR decreased mitochondrial ROS levels during differentiation. Conclusions: Our findings provide new evidence that AR contributes to intestinal epithelial differentiation and may represent a potential therapy for colorectal cancer. AdipoRon may contribute to the regulation of intestinal epithelial differentiation and may contribute to restoring epithelial homeostasis in tumor cells. Further research is needed to clarify the underlying mechanisms and assess the translational relevance of adiponectin-based therapies.