Meal times differ from culture to culture. These differences may influence energy regulation and, consequently, body weight. Current studies support the notion that not only "what" but also "when" the investigators eat may have a significant role in obesity treatment. Recently, it has been shown that eating the main meal of the day, lunch in Spain, late in the day is predictive of difficulty in weight loss and decreased insulin sensitivity. This project aims to study in a Mediterranean population the potential influence of genetics and food timing on obesity, metabolic syndrome and weight loss.

Meal times differ from culture to culture. These differences may influence energy regulation and, consequently, body weight. Current studies support the notion that not only "what" but also "when" the investigators eat may have a significant role in obesity treatment. Recently, it has been shown that eating the main meal of the day, lunch in Spain, late in the day is predictive of difficulty in weight loss and decreased insulin sensitivity. Furthermore, it has been shown that eating late at night when plasma melatonin concentrations are elevated, impairs glucose tolerance, particularly in MTNR1B risk allele carriers.

The main objective is to identify the mechanisms underlying the association between the timing of food intake, obesity and metabolic syndrome (MetS) in order to design effective weight loss therapies. The long-term goal is to determine the potential impact of more European, i.e., earlier meal timing on obesity, MetS and weight loss.

The challenge for the society is to develop evidence-based dietary interventions incorporating meal timing and genotype to combat the epidemic of obesity and MetS.

These goals will be achieved through three specific approaches:

• Epidemiological (observational study) (Aim 1): To assess in an obese population (n=5000) who will follow a weight loss program if clock-related (CLOCK, PER2, CRY, etc.) and melatonin-related variants (MTNR1B) interact with the timing of food intake to determine weight loss effectiveness and MetS features.
• Interventional (randomized controlled trials) (Aim 2): To determine the internal mechanisms of energy balance and circadian system implicated in the differential effects of food timing (lunch) on weight loss, MetS alterations and the intestinal microbiota (n=25), and to study the potential interaction between meal timing (dinner) and genetic variants MTNR1B for glucose tolerance in obese women (n=100).

Prospective Follow-up (Long-term Assessment):

We will recontact all individuals who previously participated in the ONTIME study and completed a weight-loss program at nutritional clinics at least four years ago (n=5603), aiming to achieve a final sample of approximately 500 participants. Participants will attend the nutritional clinic, where body weight, height, waist and hip circumference, and total body fat will be assessed using standardized methods. Blood samples will be collected for biochemical and genetic analyses. On the first day, participants will complete questionnaires on medical history, emotional eating, environmental factors, chronotype, sleep, physical activity, and dietary intake. All variables measured are the same as those assessed at the start of the study. Additionally, for seven consecutive days, participants will record their food intake, physical activity, and sleep using a mobile application. From this population, a subpopulation of 200 participants will undergo ambulatory ECG for three days and seven-day actigraphy and temperature monitoring using Kronosensor and a light pendant. This follow-up will allow the assessment of long-term weight loss maintenance, behavioral timing, and physiological markers several years after the initial intervention.

Inclusion Criteria:

• Body Mass Index: >25 kg/m2
• Age: >18 years of age
• Caucasian

Exclusion Criteria:

• Receiving treatment with thermogenic, lipogenic, or contraceptive drugs
• Diabetes mellitus, chronic renal failure, hepatic diseases, or cancer diagnosis
• bulimia diagnosis, prone to binge eating
• undergoing treatment with anxiolytic or antidepressant drugs

All participants are voluntarily attending five weight loss clinics in Spain for dietetic and behavioral treatment based upon the principles of a Mediterranean diet . All participants are from the Spanish city of Murcia, located on the Southeast coast of the Mediterranean Sea.