This cross-sectional study strengthens this concept that LCD with mediatory role on galactin1, TGF-beta, and PAI levels may alter the probability of depression. Remarkably, the regression model linear analysis revealed that these adipokines have mediatory role in the relation of obesity and depression.
Obesity as a gateway disease is related to higher rates of morbidity and mortality driven by its comorbidities such as nonalcoholic fatty liver disease (NAFLD), [13] diabetes [14], cancer [15], immune-mediated disorders, [16] and cardiovascular disease (CVD). Many studies indicated that obesity can be linked to depression through different pathways such as chronic inflammation. On the other, some shared disorders like CVD may be an outcome of the negative mood states or stresses in which enhance the possibility of premature mortality. Furthermore, one of the most important risk factors of myocardial infraction is determined as MDD.
Proteins secreted by adipose tissue termed adipokines have several effects on many physiological processes such as controlling the food intake, energy homeostasis, insulin sensitivity, angiogenesis, regulation of blood pressure, and blood coagulation. Visceral fat release a great amount of adipokines, including leptin, resistin, adiponectin, PAI, galactin1, and TGF-beta and is also connected to inflammation which in this manner, it is more notable than subcutaneous fat [17]. Since the association of obesity and adipokines together with metabolic disturbances are reported before, and also depression and obesity are both linked to inflammation, the importance of visceral fat as an active endocrine organ secreting different biological active components may be considered as an important issue in monitoring the inflammatory and depressive disorders [4]. Moreover, any change in adipokines levels may be a conceivable prospective regulation of obesity-depression association. However, it is not completely discovered
In the context of mood states, adipokines are involved in sending signals from adipose tissue to the brain. They straightly contribute to weight regain or predict body weight dynamics [18]. Metabolic and neuroendocrine systems and also autonomic responses are important factors related to adipokines which keep the balance of energy storage in body or cause to a constant weight loss [19]. In addition to the role of adipokines in metabolic regulation, they also work as a bidirectional communicator between adipose system and hypothalamic pituitary adrenal (HPA) axis. Moreover, their levels are reduced by the stimulatory effects of chronic or high intensity stress and also are affected by glucocorticoids and inflammatory factors. However, this conceivable association remains unknown and have not been well-defined yet.
In this manner, Taylor et al. studied the role of adipokines as anti-obesity hormones and observed that cortisol may be suggested as a pathophysiological mediator in the excess weight gain of their study population [20]. Evidence showed that weight gain and cortisol levels have mutual influence on each other. Cortisol is one of the suggested pathophysiological regulators of weight gain and has been supported by a recent study emphasizing obesity followed by the early increase of intracellular cortisol. Moreover, recent studies stated that an excessive intracellular cortisol known as pseudohypercortisolism may also happen in obesity. This could be resulted from an increase in the activation of 11β-hydroxysteroid dehydrogenase- 1 (11β-HSD-1), the enzyme which reduces cortisone to cortisol and is capable of elevating the intracellular cortisol levels in adipose tissue [21, 22]. Moreover, it was reported that the most usual biological change in obesity and MDD is dysregulation of HPA axis [23]. Indeed, the antidepressants used in the treatment of depression can affect the function of HPA axis with reducing the free cortisol levels and exacerbating the glycemic control [22].
It should be noted that adipokines can be dysregulated in mental disorders linking hypercortisolemia with signs of metabolic syndrome such as insulin resistance or visceral obesity. For instance, the association of obesity and depression through regulating adipokines has been investigated in a recent study indicating their positive correlation particularly in women. Additionally, a higher activity of HPA axis was reported in MDD patients [24] which was associated with the secretion of adipokines. Thus, previous studies showed that adipokines are affiliated with free cortisol levels in depressed patients and also are related to risk factors of insulin resistance and obesity, including BMI and QUICKI [25].
Previous studies showed the role of several adipokines such as adiponectin, leptin, and resistin in the pathophysiology of mental disorders. For instance, a study demonstrated that adiponectin levels were significantly lower in MDD patients compared to controls, while leptin levels are significantly higher [26]. In addition, the leptin insufficiency and/or leptin resistance as a predisposing agent for mental disorders like depression was also stated before. In details, a study on rats indicated that those who were exposed to chronic stress showed decreased levels of leptin followed by a depressive like behavior [27]. Anyway, despite the fact that many researchers examined the levels of adipokines in depressed people, it is an unknown matter because of the existed conflicts. Indeed, there are still some adipokines which their role in this manner is in its infancy. Hence, the present study may help us to find new discoveries about obesity and depression as one of the most important physical and psychological reason of disability in the world. Although variables such as weight, cardiovascular risk factors, medical comorbidities, and pharmacotherapies may have influences on the role of these adipokines in depression. Consequently, here, we examined the possible regulatory role of circulating PAI, galactin1, and TGF-beta as mediatory adipokines in the obesity-depression association. All the mentioned adipokines in these study regulate HPA axis in some way, therefore all of them can affect the circulating levels of cortisol.
It should be noted that weight loss due to diet and mood are related to each other with an improvement in the mood after losing weight. Food containing high proteins will produce more sense of fullness and less tiredness or sleepiness compared to food containing high carbohydrates [33, 34]. In this manner, dietary management like low calorie and fiber consumption may be effective in the regulation of adipokines levels. Remarkably, mood and mental states are related to the proportionate levels of brain-derived neurotropic factors, and are reduced by high fat diets which are likely as a consequence of corticosterone levels variations. LCD is a growing diet with high proteins and fats among people. In this diet, after emptying of glycogen stores due to the lack of dietary carbohydrate, fat oxidation is started to convert them into ketone bodies (KBs). KBs have lower efficacy but act as a fuel for body especially brain [35]. Then, they are used medically to control epilepsy and seizures. Moreover, LCD has long term effects on cognitive function in contrast to diets with enough carbohydrates. [36–38]. Therefore, in the present study, we aimed to identify the role of galactin1, TGF-beta, and PAI in depression through LCD score.
To explain our findings, randomized control trials performed by Samaha F.F. et al. and Foster G.D. et al. in 2003 indicated that LCD has a remarkable result in losing weight over a 6 to 12 months period [39, 40]. Additionally, a clinical study represented by Brinkworth G.D. et al. introduced LCD as an effective alternative dietary pattern for weight loss. The effects of LCD compared to other restricted calorie diets on fast improvement of mood are same in short terms (8 weeks) but in long terms (12 months) LCD group achieved a better outcome. Furthermore, in short terms, LCD could reduce weight more rapidly [41]. There are some suggested mechanisms for the inhibitory effect of LCD on appetite. One of them is the intake of only one class of food instead of variety of classes. Then, fewer intension and more fullness would happen after meals [42–44]. Although, more loss weight is acquired in LCD compared to low fat diet, but the mechanism for mood improvement due to LCD is still unknown. However, in a study on animal model, the antidepressant effects of LCD was observed. Then, LCD may be used as a mood stabilizer in depressive disorders [45]. In addition, glucocorticoids have some extra effects in the intake of food. An elevated tendency for consuming delicious and high calorie foods is a consequence of increased glucocorticoids levels due to chronic stress. Hence, the outcomes are an accumulation of visceral fat and a change in the levels of adipokines. A study reported that individuals following LCD had lower leptin levels compared to whom following low fat diet [46]. Here, it seems likely that galactin1, TGF-beta, and PAI adipokines produced by adipose tissue are other factors with energy-mood mediatory effects as well as leptin and adiponectin. Although, this finding are to a certain degree unclear.
Altogether, the present study demonstrated that 47.66% of obese subjects had depression which emphasize the importance of controlling obesity through diet affecting both obesity and depression. Here, for the first time we demonstrated that adipokines galactin1, TGF-beta, and PAI may act as a critical link between obesity and depression, and as a consequence, they may represent a possible novel insight in the disease monitoring and treatment. However, the relatively small number of subjects in the sample size and also investigating subjects with a same gender (256 females) are some limitations of the present study which deserve to be mentioned.