bioRxiv Science⌕ Search

Biology subjects

Zidek, L. M.

Publications and source records attributed to Zidek, L. M..

2 recordsLinked to original sources

C/EBPβ regulates hypertrophic versus hyperplastic fat tissue growth

Chronic obesity is correlated with severe metabolic and cardiovascular diseases as well as with an increased risk for developing cancers. Obesity is usually characterized by fat accumulation in enlarged - hypertrophic - adipocytes that are a source of inflammatory mediators, which is seen as causal for developing metabolic disorders. Yet, in certain healthy obese individuals fat is stored in metabolically more favorable hyperplastic fat tissue that contains an increased number of smaller adipocytes that are less inflamed. In a previous study we demonstrated that C/EBP{beta}-LIP deficient, yet C/EBP{beta}-LAP proficient mice show an expanded health and lifespan. Here we show that in mice on a high-fat diet LIP-deficiency results in adipocyte hyperplasia as well as efficient fat storage in subcutaneous depots associated with metabolic and inflammatory improvements. Our data identify C/EBP{beta} as a regulator of adipocyte fate in response to increased fat intake, which has major implications for metabolic health and aging.

physiology↗

Reduced expression of C/EBPβ-LIP extends health- and lifespan in mice

Ageing is associated with physical decline and the development of age-related diseases such as metabolic disorders and cancer. Few conditions are known that attenuate the adverse effects of ageing, including calorie restriction (CR) and reduced signalling through the mechanistic target of rapamycin complex 1 (mTORC1) pathway. Synthesis of the metabolic transcription factor C/EBP {beta} -LIP is stimulated by mTORC1, which critically depends on a short upstream open reading frame (uORF) in the C/EBP {beta}-mRNA. Here we describe that reduced C/EBP {beta} -LIP expression due to genetic ablation of the uORF delays the development of age-associated phenotypes in mice. Moreover, female C/EBP {beta}{Delta}uORF mice display an extended lifespan. Since LIP levels increase upon aging in wt mice, our data reveal an important role for C/EBP{beta} in the aging process and suggest that restriction of LIP expression sustains health and fitness. Thus, therapeutic strategies targeting C/EBP {beta} -LIP may offer new possibilities to treat age-related diseases and to prolong healthspan.

cell biology↗