Molecular Pathways Related to Short-term Fasting Response
Condition: Fasting
Study type: Interventional

Summary: 
      This study will evaluate the effect of short-term fasting (36 hours) in gene expression in
      blood cells in healthy volunteers.
    

Detailed description: 
      Fasting is a nutritional intervention consisting on the restriction of nutrient intake during
      a relatively long period of time. It elicits a profound metabolic reprogramming aimed at
      shifting nutrient supply from external food intake to internal stored nutrients. Periodic
      activation of this complex response, termed periodic or intermittent fasting (IF), elicits
      numerous protective effects against aging, metabolic alterations, neurological disorders and
      cardiovascular health. Short-term fasting is protective in different stress scenarios,
      including ischemia reperfusion, bouts of inflammation and chemotherapy-induced toxicity, and
      improves the anti-tumor efficacy of chemotherapy. Although the basic physiology of fasting is
      well known, the molecular mechanisms underlying its beneficial effects are not yet completely
      understood.

      In mammals, the response to short-term fasting (from 12 to 48 hours) in terms of nutrient
      mobilization through the bloodstream has been extensively studied. Fasting follows sequential
      phases, during which nutrients are released from different storing depots. First, glucose is
      released from glycogen stores in the liver and muscle. Upon depletion of glycogen, two
      fasting mechanisms are activated: fatty acids are exported from the adipose tissue into the
      bloodstream in the form of free fatty acids (FFAs), reaching the liver where they are used to
      produce ketone bodies, a process termed ketogenesis. Also, gluconeogenesis is activated in
      the liver, generating glucose mainly from glycerol (released during lipolysis) and amino
      acids, that originate mainly from muscle breakdown. All these physiological responses are
      tightly regulated by hormonal and molecular mechanisms.

      At the hormonal level, fasting induces a decrease in blood insulin, leptin and ghrelin, and
      an increase in glucagon levels, while blood adiponectin remains unchanged. Also, several
      signal transduction pathways are affected by fasting. PPARalpha, a nuclear receptor of fatty
      acids, becomes activated by the fasting-mediated increase in blood Free fatty Acids (FFAs)
      and triggers the expression of many target genes in several tissues, including blood cells.
      It has been shown that the Cyclin Dependent Kinase (CDK) inhibitor p21 is highly upregulated
      during short-term fasting in many mouse tissues. Moreover, it is known that p21-null mice are
      unable to endure normal periods of fasting and that p21 is required for the full activation
      of PPARa target genes both in vivo and in isolated hepatocytes.

      In the current study, the investigators wanted to study for the first time molecular
      mechanisms of fasting that still remained unexplored, specially the expression induction of
      p21 and PPARalpha signalling pathway. For this, the investigators analyzed blood samples from
      healthy volunteers subjected to 36 hours of fasting, to explore gene expression in Peripheral
      Blood Mononuclear Cells (PBMCs).
    

Intervention name(s): Fasting
Intervention type(s): Other
Intervention description(s): Food intake restriction
Intervention model: Single Group Assignment
Intervention model description: This study was an Interventional study. There were three evaluations: the basal one was an initial evaluation after overnight fasting, the second evaluation 24 hours later (36 hours fasting) and the third one 24 hours post-refeeding.
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Short-term Fasting; molecular mechanisms; p21; Peripheral blood mononuclear cells (PBMCs); PPARalpha