Impaired adipose tissue insulin signaling is a critical feature of insulin resistance. Here we identify a pathway linking the lipolytic enzyme, hormone-sensitive lipase (HSL), to insulin action via the glucose-responsive transcription factor ChREBP and its target, the fatty acid (FA) elongase, ELOVL6. Genetic inhibition of HSL in human adipocytes and mouse adipose tissue results in enhanced insulin sensitivity and induction of ELOVL6. ELOVL6 promotes an increase in phospholipid (PL) oleic acid which modifies plasma membrane fluidity and enhances insulin signaling. HSL deficiency-mediated effects are suppressed by gene silencing of ChREBP and ELOVL6. Mechanistically, physical interaction between HSL and ChREBPα, independently of lipase catalytic activity, impairs ChREBPα translocation into the nucleus and induction of ChREBPβ, the transcriptionally highly active isoform strongly associated to whole body insulin sensitivity. Targeting the HSL-ChREBP interaction may allow therapeutic strategies for the restoration of insulin sensitivity. Morigny, Houssier et al.

Protecting telomere from the DNA damage response is essential to avoid the entry into cellular senescence and organismal aging. The progressive telomere DNA shortening in dividing somatic cells, programmed during development, leads to critically short telomeres that trigger replicative senescence and thereby contribute to aging. In several organisms, including mammals, telomeres are protected by a protein complex named Shelterin that counteract at various levels the DNA damage response at chromosome ends through the specific function of each of its subunits. The changes in Shelterin structure and function during development and aging is thus an intense area of research. Here, we review our knowledge on the existence of several Shelterin subcomplexes and the functional independence between them. This leads us to discuss the possibility that the multifunctionality of the Shelterin complex is determined by the formation of different subcomplexes whose composition may change during aging.