Introduction

Ayurveda scholars have discussed both physiological as well as a pathological aspect of all the seven Dhatu i.e., Rasa (Plasma), Rakta (blood cells), Mamsa (muscle), Meda (adipose tissue), Asthi (bone), Majja (bone marrow/brain marrow), Shukra (reproductive tissue). Among these Dhatu, physiological aspect of Meda and Majja Dhatu containing mainly different adipocytes have not been extensively discussed, but their clinical physiology have been elaborated in different contexts like etiology of vitiation, pathophysiology, characteristics, and management of obesity or Sthoulya and other disorders.

Obesity is an important component of the global Syndemic, including undernutrition and climate change that affect the health and wellbeing of the people worldwide (Swinburn et al., 2019). The present epidemiological studies have reported that obesity pandemic has shifted the pattern of malnutrition in the past 40 years, which is a major risk factor for NCDs. However, after the perusal of Ayurveda literature, it seems that the obesity (Sthaulya) and disorders of fat metabolism (Meda Dushti), its impact on the functional state of other tissues and subsequent development of clinical metabolic syndrome causing Diabetes (Prameha) and NCDs have been documented in a comprehensive manner. This shows that obesity and its related disorders are not the newly emerged health problem; rather, it was present in ancient time as well. The Ayurveda, as well as recent research data, shows that this is the disorder of nutrition, which depends on lifestyle and diet.

Recent researches have given significant evidence of an association between chronic inflammation (Shopha), obesity (Sthaulya), and its subsequent disorders like diabetes, CVD, cancer, etc. The sub-inflammatory markers (cytokines) may be understood as Aama that refers to the products produced due to improper metabolism of Dhatu. Recent researches have also established various mechanisms showing how the disturbed metabolism of adipocytes affects the physiology of other tissues like bones, reproductive tissue, muscles, etc. Ayurveda scholars have also discussed these under the clinical physiology of Meda Dhatu, Majja Dhatu, and their Srotas. Thus an attempt has been done to understand the pathophysiology aspects of Meda and Majja as described in Ayurveda in light of contemporary medicine.

Materials and Methods

Ayurveda literatures were meticulously reviewed for the description of Vasa, Meda, and Majja Dhatu in different contexts like functions in different states i.e., normal, increased, decreased and vitiated, causes and features of vitiated Srotas, the pathophysiology of Sthoulya. For contemporary descriptions, most recent review articles related to the role of distinguished adipocytes in physiological as well as pathological state have been included from the electronic resources like PubMed. This article is an attempt to understand the clinical physiology of Meda and Majja Dhatu and Srotodushti in light of recent contemporary science researches.

Results and Discussion

The concept of functional and nutritional interdependence of Dhatu has been described by Ayurveda scholars (Dwivedi, Dwivedi, & Goswami, 2016). The metabolic effect of Meda and Majja Dhatu on other tissues like a muscle (Mamsa Dhatu), bone (Asthi Dhatu), and reproductive tissue (Shukra Dhatu) shows their functional interdependence (Agrawal, Verma, & Gehlot, 2019). Ayurveda scholars have not only described the physiological functions of Rasadi Dhatu and the mechanism of tissue nutrition (Dhatu Poshan) but also mentioned the manifestation of signs and symptoms in case of disturbed physiology. The obesity has been discussed in relation to Medovaha Srotodushti and Meda Dhatu Vriddhi (Thakarar, 2017).

Although the physiology of Vasa, Meda, and Majja tissue have not been elaborated much but their clinical physiology have been described i.e., the symptoms manifested in their increased or decreased or vitiated state, factors causing vitiation of their Srotas, description of Srotasmoola, etc. (Table 1). These symptoms can be interpreted through the recent advancement in the field of adipocytes to understand the role of these tissues in the maintenance of homeostasis and manifestation of pathology.

Consideration of kidney (Vrikka), omental/visceral fat (Vapavahana), waist area (Kati) and Mamsa (muscle) as Srotomoola of Medavaha Srotas

The Srotomoola are the primary sites of onset of pathogenesis or the organ through which disease signs and symptoms of a particular Srotas get manifested (Dwivedi et al., 2016; Verma & Gehlot, 2014). These organs, too, have an important role in pathophysiological conditions related to adipose tissue. The possible reasons behind consideration of these as Srotomula of Medavaha Srotas are described in Table 2 . Meda has also been considered as Moola of Asthivaha Srotas while Majja as Moola of Shukravaha Srotas. Recently, it has been found that osteoclastin secreted by bone affects fat metabolism and insulin sensitivity (Karsenty G et al., 2016), thus affecting the functions of adipose tissue. (Acharya, 2008; Dwivedi et al., 2016; Thakarar, 2017)

Manifestations of an abnormal state of Meda Dhatu

Features of Sthoulya, Meda Vriddhi, and Meda Dushti have been mentioned to describe the pathophysiology of the abnormal functional state of Meda. Obesity has been defined as a cluster of symptoms of increased Meda and Mamsa Dhatu, increased adiposity in buttock, breast, and abdomen, decreased body strength (Dwivedi, Dwivedi, & Goswami, 2016). It manifests eight peculiar features i.e., short life span, early aging, sexual dysfunction, debility, profuse sweating, foul smell, feeling of excessive hunger, and thirst (Dwivedi et al., 2016). The features of increased Meda include increased waist circumference (increased visceral fat in abdominal region), cardiorespiratory disturbance and foul smell due to excessive sweating (Thakarar, 2017) while vitiated Meda includes excessive sweating (Atisweda), inflammation (Shopha), prodromal symptoms of diabetes (Prameha poorvaroop) and thirst dysregulation (excessive thirst and dryness in palate)

(Dwivedi et al., 2016; Thakarar, 2017), These might be included under different clusters of symptoms of metabolic syndromes, which also depicts disease advancement. (NCEP, 2001) has defined metabolic syndrome as a cluster of three or more of the following: abdominal obesity, elevated blood pressure, impaired fasting glucose, elevated triglyceride, and decreased high-density lipoprotein (HDL) cholesterol level. It is linked with an increased risk of cardiovascular disease (CVD) and type 2 diabetes (Eckel, Grundy, & Zimmet, 2005).

Pathophysiology of Sthoulya

Dietary and lifestyle factors causes vitiation of Medadhatvagni, which will leads to overproduction of Meda Dhatu while disturbing the nourishment of other Dhatu, obstruction of channels (Srotas) leading to Vataprakopa which repetitively augments Jathragni (digestive power) making a person more and more desirous for eating. Vitiated Medo Dhatavagni will also lead to the productions of Aama, which circulates in the whole body, affecting the metabolism as well as nourishment of other Dhatu. These factors produce a circumstance of over nourishment of Meda Dhatu and undernourishment of other Dhatu (Dwivedi, Dwivedi, & Goswami, 2016; Shrikanth, Nidan, & Vijayarakshita, 2009).

The whole mechanism can be understood from the different manifestation of obesity as described in Figure 1.

(Akhmedov & Berdeaux, 2013; Cao, 2011; Crujeiras & Casanueva, 2015; Jungheim, Travieso, Carson, & Moley, 2012; Mansour et al., 2017; Nagpal et al., 2018; Oussaada et al., 2019; Patel, Chan, Rubin, & Rubin, 2018; Romeo, Lee, & Shoelson, 2012; Simonds, Cowley, & Enriori, 2012).

Parameter for assessing obesity

Different parameters like BMI, waist circumference, waist-hip ratio, total body fat, etc. are employed for the assessment of obesity. Among these waist circumferences is mostly used as a reliable method. In Ayurveda, simile of pork has been narrated to refer physique of an obese, as the deposition of fat occurs mainly on trunk region i.e., gluteal, abdomen, and breast; thus, it describes the central obesity, which is assessed through waist-hip ratio circumference. As prevention of obesity has become a global challenge now a days, different obesity models are prepared in laboratories, then altered cellular functions with the help of diverse biochemical parameters are analyzed. In Ayurveda, the overall effect of obesity on human life have been mentioned, which are outcomes of the present researches too. Table 3 summarizes eight peculiar features of obesity as described in Ayurveda with support of findings evidence-based researches and probable hypothesis (Dwivedi et al., 2016).

Effect of Sthoulaya or Meda Vriddhi on bone metabolism: Ayurveda Scholars have opined that Meda Dhatu in its normalcy state provides nourishment to Asthi Dhatu (Thakarar, 2017) but when it gets increased it results in Asthi Kshaya (Thakarar, 2017). Contemporary researches, too have found that secretion of adipocytes maintains the nourishment of bone tissues in normalcy, but in case of obesity, they unfavorably disturb the bone metabolism through several ways (Cao, 2011) as described in Figure 2.

Effect of decreased and increased state of Majja Dhatu

Increased status of Majja Dhatu results in heaviness in whole body including eyes (Sarvanaganetragauravam) (Thakarar, 2017) while decreased status results in low fertility (Alpashukrata), joint pain (Parvabheda), bone pain (Asthinistoda), lightness, thinness and weakness of the bones, osteoporosis (Asthishunyata), affliction with Vata disorders continuously (Dwivedi et al., 2016; Thakarar, 2017).

Affliction with continuous Vata disorders (Pratata Vatarogani) might be indicating dysregulated neural activities either due to osteoporotic changes resulting in imbalanced serum calcium ion concentration or loss of lipid covering of neurons resulting in their hyper excitability. Secondly, this description might be pertaining to injury or degeneration of Mashtaka Majja under which central and peripheral tracts can be taken, leading to the onset of features like a cramp, paresthesia, etc. The features in the disturbed state of Majja Dhatu need more exploration through evidence-based research as some of these are not in consistence with contemporary researches, for example, a study by (Li, Meng, & Yu, 2019) have shown that increased bone marrow adipocytes results in the manifestations like osteoporosis, decreased bone mineral density, but it has been described under the increased conditions of bone marrow adipocytes as per Ayurveda (Li et al., 2019; Paccou, Penel, Chauveau, Cortet, & Hardouin, 2019).

Secondly, a manifestation of heaviness in the whole body including eye in the increased status has been interpreted as an increased amount of circulation RBCs resulting in polycythemia and by some authors but recent researches are not in consistence with the positive correlation of increased bone marrow adipocytes and haemopoisis (Wang, Leng, & Gong, 2018). Thirdly bone marrow has been shown to induce spermaetogenesis in azoospermic hamsters (Karimaghai et al., 2018), but its other role in reproductive functions is not clear.

Ayurveda scholars have mentioned that bone marrow adipocytes (Majja Dhatu) are responsible for immunity (Bala), mental attributes (Sneha, Preeti), nourishment of reproductive functions, and filler of bone (Asthipurana) (Thakarar, 2017). Recent researchers have shown that bone marrow adipocytes are not only the filler of bone but having a great role in homeostatic functions of the body. However, more studies are required to evaluate the relationship of bone marrow fat with other homeostatic functions of the body, especially mental attributes.

Conclusions

The concept of functional and nutritional interdependence of Dhatu has been described by Ayurveda scholars. Obesity is primarily a disorder of Meda Dhatu Dushti that causes malnutrition of other tissues leading to multiple dysfunctions at the level of different tissues. The metabolic effect of Meda and Majja Dhatu on other tissues like a muscle (Mamsa Dhatu), bone (Asthi Dhatu), and reproductive tissue (Shukra Dhatu) shows their functional interdependence which is consistent with the recent research findings of contemporary science.

The researchers are trying to find out the consequences of obesity, the role of adipocytes in the development of state of metabolic syndrome with various hypotheses. This manuscript will provide to researchers an insight about the Ayurveda understanding about a clinical physiological aspect of Meda, Majjja Dhatu, Shrotodushti, obesity, and consequent disorders and may help in further exploration of the role of adipocytes and other tissues in the development of the metabolic syndrome and NCDs. The whole discussion elucidates that Ayurveda scholar had a profound understanding about the clinical physiology of Meda and Majja Dhatu. Pathophysiology of Sthoulya described by them also reflects their deep insights in the manifestation of metabolic syndromes.

Although some views, for example, the effect on bone metabolism, are not consistent with findings of contemporary researches while some likes relation of bone marrow with mental attributes, the occurrence of deep-seated eruptions on vitiated Majja Dhatu needs more research for their significance.