Time-Restricted Feeding and Weight Loss in Obesity: Comparison
Please note this is a comparison between Version 1 by José Rodrigo Pauli and Version 2 by Dean Liu.

Across the globe, obesity is a significant concern for public health, a disease characterized by excessive accumulation of body fat, with a negative impact on health. Time-restricted feeding (TRF), in which food accessibility is restricted to a variable period of 8–10 h, especially in the active phase, inducing a prolonged fasting period, is a strategy with potential effects in preventing obesity. Evidence in preclinical studies demonstrated that TRF attenuates the impacts of metabolic disturbances related to high-fat diet feeding in rodents. Through these discoveries, there has been growing interest in revealing the effects associated with TRF in preventing obesity and its comorbidities, as well as investigating its effects in humans. Although TRF is a promising alternative to reduce the impact of obesity, it is necessary to investigate the results on skeletal muscle tissue. Muscle tissue is important for body energy expenditure; however, caloric restriction can negatively impact protein turnover and induce loss of muscle mass, influencing the basal metabolic rate and weight loss.

  • obesity
  • intermittent fasting
  • skeletal muscle
  • protein turnover

1. Introduction

The prevalence of obesity is a global public health problem with multifactorial etiology, including genetic, physiological, sociocultural, economic, and environmental factors [1]. Obesity is linked to numerous enduring health disorders, such as diabetes, hypertension, non-alcoholic fatty liver disease (NAFLD), cardiovascular disease, and various cancer types, as well as non-metabolic complications, including anxiety and depression [1].
Despite its constraints, addressing the health consequences of conditions associated with obesity often involves promoting weight loss to enhance both individual health and that of the population. However, weight loss achieved through restrictive diets triggers physiological and psychological “homeostatic pressures”, contributing to weight regain in over 90% of individuals [1].
In recognition of the limited effectiveness of restrictive dietary approaches with low long-term adherence, increasing emphasis has been placed on intermittent fasting nutritional strategies with time-restricted feeding (TRF). TRF is a fasting strategy with great applicability, showing excellent results for individuals who face difficulties in adhering to caloric restriction and who fear the possible side effects that a pharmacological treatment protocol may present [2][3][4][2,3,4].
It is established that obesity is correlated with impairments in muscle performance, resulting in an increased risk of developing functional disabilities, encompassing limitations in mobility, strength, postural control, and dynamic balance [5]. A possible negative result of TRF as a strategy to combat obesity could be the inhibition of muscle protein synthesis induced by post-prandial stimulation. As TRF decreases food intake, including protein, for some time, there is a hypothesis that this strategy could lead to a negative nitrogen balance and, consequently, to loss of muscle mass [6][7][6,7].

2. Time-Restricted Feeding

Intermittent fasting has been applied as an important tool for treating obesity and related diseases. This feeding protocol comprises several different forms of food intake, such as daily or weekly intake. Among the protocols studied, the three most relevant comprise complete fasting on alternate days (ADF): which involves deprivation of food on alternate days (fasting on days); modified alternating diets (MADF): which adopts different variations of ADF; and finally, time-restricted feeding (TRF): where food intake is restricted to specific times, with fasting for a long period. The scientific literature considers TRF as one of the most widely practiced fasting strategies to improve health and body composition through caloric restriction. TRF can range from 4 to 12 h, but an 8 h feeding period with a daily 16 h fast is typical [8][9][8,9]. Unlike most forms of intermittent fasting (IF), TRF does not necessarily have to be performed with a reduced caloric intake, as the potential benefits are linked to the time of day when the meals will be completed. The influence of the circadian system could explain the time-dependent effects observed in TRF interventions. The energy metabolism of glucose and lipids is regulated by the circadian cycle, which has an up and down regulation at different times of the day. For example, in humans, insulin sensitivity and the thermic effect of food exhibit greater prominence in the morning compared to the afternoon or evening. This observation implies that energy metabolism is optimized for food consumption during the daytime [10]. In a study conducted by Keim et al. (1997) involving women following a controlled weight-reduction regimen, it was observed that consuming the main meal in the morning (AM) resulted in more significant weight loss in comparison to finishing it in the evening (PM) [2]. Furthermore, consuming the main meal in the morning was associated with improved preservation of lean body mass. Thus, incorporating PM meals in a weight loss program may play a crucial role in reducing the loss of fat-free mass. However, for meals aligned with the circadian rhythm, increasing morning food intake may be more effective for weight loss [11]. This finding indicates that the efficacy of TRF interventions may rely on distinct mealtime strategies, necessitating different approaches for each specific objective.

3. TRF and Obesity

Lifestyle changes are the basis for obesity prevention and treatment strategies. These alterations include decreasing energy intake to approximately 500 kcal, increasing physical activity, and behavioral change techniques. Conventional calorie-restricted diets may have limited long-term success, with adherence levels typically lasting for 1 to 4 months, followed by significant weight regain in approximately one year [12]. As a way of preventing and treating obesity, TRF has been used as a fasting strategy with great applicability, offering a variety of nutritional therapy options for those who face difficulties in adhering to caloric restriction and who are concerned about possible side effects derived from a pharmacological treatment protocol. Preclinical studies provided scientific evidence demonstrating that the implementation of TRF can offer protection to obese rodents that are fed a high-fat diet. This protection is manifested through mitigated increases in body adiposity and reduced endocrine-metabolic disorders [13][14][15][16][17][13,14,15,16,17]. In this context, Hatori et al. (2012) studied whether obesity and metabolic diseases are due to a high-fat diet (HFD) or the interruption of metabolic cycles. For this, mice were fed ad-lib for 8 h TRF in the dark phase of an HFD for 8 h a day. Consequently, the researchers noted that mice following the TRF regimen consumed a similar amount of HFD calories as those with unrestricted access. However, the TRF group exhibited protection against obesity, hyperinsulinemia, fatty liver, and inflammation. A study by Olsen et al. (2017) reported that animals with obesity induced by a high-fat diet submitted to a TRF regimen presented a restriction in weight gain when compared to free-fed animals, despite the same caloric intake levels. TRF also efficiently prevented excessive weight gain and metabolic diseases in mice without a circadian cycle in a food access protocol restricted to 10 h during the dark phase [10]. Overall, current evidence is positive, as TRF is associated with decreased body weight, improved glycemic homeostasis and insulin signaling, reduced inflammation, and a favorable effect on dyslipidemia [14][17][18][19][14,17,18,19]. Studies have also shown that TRF can prevent the development of NAFLD [10][13][20][21][10,13,20,21]. Following from the success of the effects of TRF when applied to animals, studies were developed using this dietary strategy in humans, which also showed efficient results in obesity. This fact was observed by Cienfuegos et al. (2020), where obese adults on a TRF protocol ranging from 4 to 8 h over 8 weeks successfully reduced weight, insulin resistance, and oxidative stress versus controls [22]. Positive data were also verified in a study by Jamshed et al. (2022), in obese individuals, where an 8 h food window was more effective for weight loss when compared to a group that performed a conventional food restriction protocol for 12 weeks [8]. In a study by He et al. (2022), the effects of a low-carbohydrate diet (LCD), an 8 h TRF protocol, and their combination were investigated over three months on body weight and abdominal fat area. The LCD treatment and the 8 h TRF protocol significantly reduced body weight and the subcutaneous fat area. However, only the TRF and the combined intervention reduced the visceral fat area (VFA), fasting glucose levels, uric acid (UA) levels, and improvements in dyslipidemia. In conclusion, an 8 h TRF can be regarded as an effective therapeutic approach for addressing metabolic syndrome [23]. Even with the benefits mentioned above, there are concerns regarding TRF and muscle mass homeostasis. A deficiency in caloric and protein intake can have a catabolic effect, in which degradation is more significant than protein synthesis, inducing loss of muscle mass. A possible negative result of TRF could be the inhibition of muscle protein synthesis induced by post-prandial stimulation.
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