**3. Mechanisms suggested for VDD in obesity**

Several studies have shown the relationship between obesity and inadequacy of VD [56–58]. Evidence suggests that one of the VDDs in subjects with obesity may be connected to storage of VD in the adipocytes, reducing its bioavailability and activating the hypothalamus to develop a cascade of reactions that result in increased feelings of hunger and decreased energy expenditure [59]. Low serum of 25(OH)D concentrations is found to be inversely correlated with measures of obesity, including body mass index (BMI) (≥30kg/m2 ), fat mass, and WC [60, 61]. A bidirectional genetic study has suggested that higher BMI chiefs to lower 25(OH)D; each unit increase in BMI is being associated with 1.15% lower concentration of 25(OH)D, after adjusting for age, sex, laboratory collection, and month of measurement [62]. The relationship between obesity and 1,25(OH)2D is less clear, and this is probably due to the dynamic nature of the production and regulation of the active hormone. However, the study in vitro showed that 1,25(OH)2D acts as a potent inhibitor of leptin secretion in a culture of human adipocytes [63].

Extensive evidence has demonstrated that adipocytes become enlarged and dysregulated the following weight gain, which subsequently produces an imbalance in the inflammatory profile of AT. So, obesity is commonly linked to an upregulation of pro-inflammatory molecules and downregulation of anti-inflammatory molecules [64]. Individuals with both high SAT and high VAT have an approximately threefold prevalence of VDD compared with those with both low SAT and low VAT [34]. A predominant effect of VD on macrophages could explain the differences observed in relations of VD response in VAT versus SAT. Is observed a greater macrophage infiltration of VAT when compared with SAT in individuals with obesity. In contrast, inflammatory markers in AT strongly correlate with macrophage infiltration [65], and many metabolic differences could potentially explain the different VD-induced anti-inflammatory response observed between these two types of AT, including the number of cells expressing the VDR [52]. Because ATs of obese are infiltrated with macrophages, it seems likely that macrophages also contribute to the local activation of VD. Because SAT and BMI are closely correlated, it is possible that most of the association between SAT and 25(OH)D is attributable to the difference in body size that is seized by BMI. It is observed that lower 25(OH)D was associated with greater regional adiposity.

In fact, the basis of low concentration in subjects with obesity is not totally known but could be the result of various mechanisms. There are five suggested mechanisms that are most commonly cited within the literature which may explain a low VD status in obesity:


**•** *Negative feedback control*.

CYP2J2 is more prominent in SAT than in VAT in lean women. So, these findings lead to a compromised of 25-hydroxylation in SAT in obese, taken by a lower expression of the CYP2J2.

Several studies have shown the relationship between obesity and inadequacy of VD [56–58]. Evidence suggests that one of the VDDs in subjects with obesity may be connected to storage of VD in the adipocytes, reducing its bioavailability and activating the hypothalamus to develop a cascade of reactions that result in increased feelings of hunger and decreased energy expenditure [59]. Low serum of 25(OH)D concentrations is found to be inversely correlated

61]. A bidirectional genetic study has suggested that higher BMI chiefs to lower 25(OH)D; each unit increase in BMI is being associated with 1.15% lower concentration of 25(OH)D, after adjusting for age, sex, laboratory collection, and month of measurement [62]. The relationship between obesity and 1,25(OH)2D is less clear, and this is probably due to the dynamic nature of the production and regulation of the active hormone. However, the study in vitro showed that 1,25(OH)2D acts as a potent inhibitor of leptin secretion in a culture of

Extensive evidence has demonstrated that adipocytes become enlarged and dysregulated the following weight gain, which subsequently produces an imbalance in the inflammatory profile of AT. So, obesity is commonly linked to an upregulation of pro-inflammatory molecules and downregulation of anti-inflammatory molecules [64]. Individuals with both high SAT and high VAT have an approximately threefold prevalence of VDD compared with those with both low SAT and low VAT [34]. A predominant effect of VD on macrophages could explain the differences observed in relations of VD response in VAT versus SAT. Is observed a greater macrophage infiltration of VAT when compared with SAT in individuals with obesity. In contrast, inflammatory markers in AT strongly correlate with macrophage infiltration [65], and many metabolic differences could potentially explain the different VD-induced anti-inflammatory response observed between these two types of AT, including the number of cells expressing the VDR [52]. Because ATs of obese are infiltrated with macrophages, it seems likely that macrophages also contribute to the local activation of VD. Because SAT and BMI are closely correlated, it is possible that most of the association between SAT and 25(OH)D is attributable to the difference in body size that is seized by BMI. It is observed that lower 25(OH)D was

In fact, the basis of low concentration in subjects with obesity is not totally known but could be the result of various mechanisms. There are five suggested mechanisms that are most

commonly cited within the literature which may explain a low VD status in obesity:

**•** *Obese individuals have reduced sun exposure compared with lean subjects*.

), fat mass, and WC [60,

**3. Mechanisms suggested for VDD in obesity**

148 Adiposity - Omics and Molecular Understanding

human adipocytes [63].

associated with greater regional adiposity.

**•** *Low 1*.*25*(*OH*)*2D inhibits adipogenesis*.

with measures of obesity, including body mass index (BMI) (≥30kg/m2


#### **3.1. Reduced sun exposure**

Obese individuals reduce their exposure to sunlight, reportedly have a limited mobility, avoid performing outdoor activities, and/or use clothes that cover more of the body [56], which limit exposure to the sun and, consequently, cutaneous VD synthesis. However, in a study based on the Framingham cohort, which evaluated the association between obesity and VD, it was reported that after adjustments for practicing outdoor physical activities, this theory was insufficient to explain the relationship between obesity and VDD [34]. In addition, the study indicates that daily exposure to 0.5 standard erythemal dose (SED) between 11:00 and 13:00h, using typical summer clothing, was not enough to achieve the state suitable of VD in the late summer [66]. Until now, it is still unclear which VD supplementation dose corresponds to the amount of UVB radiation exposed, in regard to efficiency to increase serum concentrations of 25(OH)D and as little establishing a standard exposure solar time daily necessary to achieve an adequate state of VD [67].
