Multi-generational effects of lindane on nematode lipid metabolism with disturbances on insulin-like signal pathway.

Abstract Influences on lipid metabolism and multi-generational obesogenic effects raised new concerns on lipophilic pollutants (e.g., lindane). Yet, the mechanisms remained unanswered. The present study exposed Caenorhabditis elegans to lindane for 4 consecutive generations (F0 to F3) at 1.0 ng/L, and measured effects in the directly exposed generations (F0 to F3), indirectly exposed ones (T1 and T1′) and un-exposed ones (T3 and T3′). Lindane stimulated fat storages in all generations. At the biochemical level, lindane stimulated both acetyl-CoA carboxylase (ACC) and carnitine palmitoyl-transferases (CPT) in F0, T1 and T2, while inhibited them in F3, T1′ and T3′, demonstrating the balance between fatty acid synthesis and its depletion toward fat accumulation over generations. Moreover, lindane caused different effects on insulin among generations. It inhibited insulin in F0 and F3 and exhibited consistent effects on the expression changes of daf-2 , sgk-1 and daf-16 genes in insulin-like signal pathway. Lindane also inhibited insulin in T1 and T3 but exhibited consistent effects on the expression changes of daf-2 , akt-1 and daf-16. Different roles of sgk-1 and akt-1 indicated the response strategies from tolerance (F0 and F3) to avoidance (T1 and T3). Lindane stimulated insulin in T1′ and T3′ and exhibited consistent effects on expression changes of daf-2 , sgk-1 and daf-16 genes that were similar in F0 and F3. Highlights • Multigenerational obesogenic effects of lindane were studied on C. elegans. • Lindane stimulated fat storages in F0, F3, T1, T3, T1′ and T3’. • Fat storage stimulation was due to greater fatty acid synthesis than its oxidation. • Lindane inhibited insulin in F0, F3, T1 and T3, but stimulated them in T1′ and T3’. • Insulin changes were consistent with expressions of daf-2 , sgk-1 / akt-1 and daf-16. [ABSTRACT FROM AUTHOR]