Metabolic Investigation, Physical Performance, Physical Training At Different Times of the Day in Obese Women

Obesity is a disease characterized by the accumulation of adipose tissue, which is multifactorial and can be caused by environmental, social, behavioral, biological and genetic issues, and affects people health and well-being. In this sense, it is still difficult to maintain an effective treatment for obesity, since currently in Brazil, 24% of the population is obese and 61% is overweight. Physical exercise is considered a component that promotes numerous benefits to the human body, by releasing molecules through muscle contraction that will travel throughout the body as a whole, resulting in benefits such as increased energy expenditure and, consequently, improved physical performance, which will influence a person\&amp;amp;amp;amp;amp;#39;s daily activities. However, the effects of physical exercise depend on some factors, such as the time and duration of the practice. In addition, the changes that occur in the body can be influenced by the time of day. Likewise, it is known how important it is to maintain adequate sleep duration at night. It is possible that the time of day when exercise is practiced influences the responses that occur in the human body. To understand this fact, obese women will undergo combined physical training (strength and aerobic exercises) performed in the morning and evening. The aim is to better understand the time of day for controlling the metabolism of obese people. And, if there is a time when people perform better in daily activities.

Therefore, the objective of this clinical trial is to evaluate whether the time of day influences the responses to combined physical training in the modulation of energy metabolism and its biochemical markers in obese women. The main questions to be answered are:

1. Can combined physical training (CPT) performed at night have different metabolic responses than CPT in the morning?
2. Can cardiopulmonary and muscular strength performance have different magnitudes of responses to CPT performed at different times of the day?
3. Can combined physical training (CPT) in the evening (NOT) compared to the morning (MAT) period cause more marked physiological adaptations, improving metabolic control in women with obesity?

Obesity is a chronic, non-communicable, neuroendocrine and nutrimetabolic disease with multifactorial development, which results in a positive energy balance and excessive accumulation of adipose tissue. Characteristics of its metabolic profile include changes in mitochondrial architecture and in the secretion of hormones, such as insulin, which controls glucose metabolism. In obese individuals, adipocytes can undergo hypertrophy and hyperplasia processes, inducing low-grade inflammation. Conventional treatment for obesity consists of a hypocaloric diet combined with increased physical activity aimed at achieving a negative energy balance. However, the failure of these measures has highlighted the need for metabolic studies and studies of factors that may influence non-pharmacological treatments, such as physical training.

Physical training can improve the lipid profile of obesity, reducing cholesterol, trimethylamine N-oxide and sphingolipids, which are associated with risk factors for cardiovascular morbidity caused by obesity. An intervention with combined physical training (CPT) for 8 weeks can reduce waist circumference and increase maximum oxygen consumption in women with obesity. This approach can improve physiological functions that are altered due to obesity, such as hormonal control and bioenergetic efficiency, impacting physical fitness, regardless of weight loss. These improvements may arise depending on the configuration of the training load components, such as frequency, intensity, volume, repetition duration, pause and total session time, since it is a modifiable aspect and its manipulation provides different physiological responses.

In this sense, another factor to be considered is the circadian rhythm, which acts on metabolic regulation, and considering its functions it is assumed that it can influence the treatment of metabolic disorders, such as obesity, and physical performance. It is a biological event in which organisms go through the sleep-wake cycle, characterized by a 24-hour period that includes variations in physiological functions such as body temperature, sleep, physical activity, mood and cognition.

There are different sleep patterns and times for performing daily activities. Chronotype is a terminology that refers to the individual expression of circadian rhythmicity, a factor that is related to preferences for sleep time and duration, diet, and physical activity patterns, including exercise. Chronotype can be classified as: morning, intermediate, and evening. Based on this information, the circadian rhythm has been suggested as an influencer on responses to physical training. This biological clock can be impaired in people with metabolic disorders, such as obesity, while physical training can help regulate this clock. Several studies in humans and rodents have revealed that variables such as skeletal muscle strength and capacity demonstrate significant differences throughout the day. Therefore, this study hypothesizes that combined physical training, in the evening (NOT), compared to the morning (MAT), will cause more marked physiological adaptations, improving metabolic control, in female mice and women with obesity.

Thus, the general objective of the study will be to evaluate the effects of Combined Physical Training (CPT) performed in the morning versus evening on the remodeling of muscle and adipose tissue, metabolism and physical performance in women with obesity.

While the specific objectives:

1. To evaluate in women with obesity, before, during and after the intervention with morning TFC and evening TFC: 1.1. Body composition and body thermography; 1.2. Resting energy expenditure and oxidation of substrates (carbohydrates and lipids); 1.3. Food consumption; 1.4. Physical performance (muscular and aerobic strength); 1.5. Behavioral measures of sleep (sleep duration; sleep latency; habitual sleep duration and efficiency; circadian sleep quality and typology; daytime sleepiness); 1.6. Plasma metabolome by UPLC-MS. 1.7. Hormone levels in peripheral blood (cortisol, melatonin, corticotropin-releasing hormone - CRH, and adrenocorticotropic hormone - ACTH); 1.8. The level and phase of gene expression of the circadian cycle in peripheral blood (BMAL1, CLOCK, Cry1 and 2, Per1-3) and of energy metabolism in peripheral blood (PGC-1α, PPARγ, PPARα, NR1D1); 1.9. Verify the concentration of anti- and pro-inflammatory cytokines and myokines in peripheral blood (IL-1, IL-6, TNF-α, IL-10, IL-15 irisin, adiponectin, BNDF);

Therefore, this is an exploratory, prospective and longitudinal study, which will be carried out at the Laboratory of Research in Metabolism, Physiology and Physical Exercise of the State University of Minas Gerais, Divinópolis unit, Minas Gerais, Brazil. The sample size calculation was performed based on an equation. To perform the calculation, the chosen variable was physical performance, and data from the work of Bruggisser, was used as a source. The significance level adopted was 5%, the test power was 90%, the standard deviation was 0.80 W/kg and the difference to be detected was 0.51 W/kg. The calculation showed the need for 10 participants in each experimental group, assuming a possible loss of 20% throughout the study, the sample will consist of 12 participants per group, totaling 36 individuals of the biological female sex.

The study will last a total of 12 weeks. After verifying whether the people who have shown interest meet the inclusion criteria, they will undergo a period of anthropometric assessments, body composition, energy metabolism, blood sample collection, familiarization with the training protocol and physical tests, 2 weeks before the TFC intervention. After the TFC intervention, which will last 8 weeks and be performed 3 times a week, the same series of assessments and physical tests will be repeated for 2 weeks. Also, throughout the study, food consumption will be monitored through 24-hour recalls, and participants will be advised not to change their usual diet.

Eligibility Criteria:
Inclusion Criteria:

* Women aged between 20 and 45 years
* not practicing physical exercise
* body mass index between 30 and 39.9 kg/m²
* without any positive response when filling out the risk stratification questionnaire

Exclusion Criteria:

* Cardiovascular comorbidity
* joint and neuromuscular injuries
* diseases that affect visual and auditory functions
* disorders related to the sleep and wake cycle
* dependent on the use of psychoactive drugs
* drug treatment that influences sleep
* drug weight loss treatments
* previous bariatric surgery
* illness during the project period
* night shift workers
* attendance of 90% of the intervention with physical training