Social isolation alters the adipocyte secretome and impairs insulin signaling in obese male mice
Description
Chronic social isolation is a psychosocial stressor known to disrupt metabolic homeostasis, particularly under obesogenic conditions. We hypothesized that social isolation alters the adipocyte secretome in obese male CD1 mice, leading to increased insulin resistance in recipient cells. Male CD1 mice were fed a high-fat diet and housed in either group (3/cage) or isolated (1/cage) conditions for 8 weeks. Visceral adipose tissues were collected, cultured, and used to generate adipocyte conditioned media (ACM). CHO-IR cells were incubated with ACM and subsequently stimulated with insulin. Insulin signaling was quantified via In-Cell Western analysis of phosphorylated Akt levels.
Conditioned media from socially isolated mice significantly decreased insulin-stimulated Akt phosphorylation in CHO-IR cells compared to group-housed controls, indicating reduced insulin sensitivity. In vivo, isolated mice displayed significantly higher fasting insulin levels and HOMA-IR scores, despite no difference in fasting glucose. RNA sequencing revealed depot-specific transcriptional changes, with several inflammation and metabolism pathways upregulated in adipose tissue from isolated mice.
These findings suggest that social isolation reprograms the adipocyte secretome in a way that impairs downstream insulin signaling, independent of changes in glucose levels. Further investigation into key secreted factors and regulatory genes, such as Rps2-ps10, which is significantly downregulated in isolated mice, may yield therapeutic targets for stress-induced insulin resistance.
Citation Information
Burau, Sarah; Piron, Matthew; Caraveo, Jacquelyn; and Brady, Matthew, "Social isolation alters the adipocyte secretome and impairs insulin signaling in obese male mice" (2026). Office of Research DMU Research Symposium. 52.
https://digitalcommons.dmu.edu/researchsymposium/2025rs/2025abstracts/52
Social isolation alters the adipocyte secretome and impairs insulin signaling in obese male mice
Chronic social isolation is a psychosocial stressor known to disrupt metabolic homeostasis, particularly under obesogenic conditions. We hypothesized that social isolation alters the adipocyte secretome in obese male CD1 mice, leading to increased insulin resistance in recipient cells. Male CD1 mice were fed a high-fat diet and housed in either group (3/cage) or isolated (1/cage) conditions for 8 weeks. Visceral adipose tissues were collected, cultured, and used to generate adipocyte conditioned media (ACM). CHO-IR cells were incubated with ACM and subsequently stimulated with insulin. Insulin signaling was quantified via In-Cell Western analysis of phosphorylated Akt levels.
Conditioned media from socially isolated mice significantly decreased insulin-stimulated Akt phosphorylation in CHO-IR cells compared to group-housed controls, indicating reduced insulin sensitivity. In vivo, isolated mice displayed significantly higher fasting insulin levels and HOMA-IR scores, despite no difference in fasting glucose. RNA sequencing revealed depot-specific transcriptional changes, with several inflammation and metabolism pathways upregulated in adipose tissue from isolated mice.
These findings suggest that social isolation reprograms the adipocyte secretome in a way that impairs downstream insulin signaling, independent of changes in glucose levels. Further investigation into key secreted factors and regulatory genes, such as Rps2-ps10, which is significantly downregulated in isolated mice, may yield therapeutic targets for stress-induced insulin resistance.
