Molecular Pathways Related to Short-term Fasting Response

IMDEA Food

Status

Completed

Conditions

Fasting

Treatments

Other: Fasting

Study type

Interventional

Funder types

Other

Identifiers

NCT04259879

IMD PI0025

Details and patient eligibility

About

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

Full 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).

Enrollment

20 patients

Sex

All

Ages

18 to 50 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Men and women between 18 - 50 years old.
BMI >20<30
Adequate education level and comprehension of the clinical study
Willingness to participate in the study as a volunteer and to provide written consent

Exclusion criteria

BMI <20 (thinness)
BMI >30 (obesity)
Abnormal low glucose levels after fasting
Having donated blood less than 8 weeks before starting the study
Subjects who report special discomfort after previous periods of short fasting
Diagnosis of type 2 Diabetes mellitus (insulin-dependent)
Dyslipidemia under pharmacological treatment
High blood pressure under pharmacological treatment
Dementia, neurological disease or reduction of cognitive function
Severe illness (hepatic disease, renal disease, etc
Taking medications that could affect the lipid and glycemic profiles (statins, fibrate, diuretics, corticoids, anti-inflammatory, hypoglycemic or insulin) 30 days before the beginning of the study.
Taking medications or substances for weight loss management (15 days before the beginning of the study)
Pregnancy or lactation