Yoga Training Modulates Adipokines in Adults with High- Normal Blood

Accepted: 28 November 2017

DOI: 10.1111/sms.13029

ORIGINAL ARTICLE

Yoga training modulates adipokines in adults with high-normal blood pressure and metabolic syndrome

1Department of Health Technology and Informatics, Faculty of Health and Social Metabolic syndrome (MetS) is associated with diabetes mellitus and cardiovascular Sciences, The Hong Kong Polytechnic diseases. Our previous study indicated that people with MetS showed a decrease in University, Kowloon, Hong Kong, China waist circumference and a decreasing trend in blood pressure after 1-year yoga. This 2 School of Public Health, Li Ka Shing study investigated the effect of yoga on MetS people with high-normal blood pres- Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China sure by exploring modulations in proinflammatory adipokines (leptin, chemerin, vis- 3School of Nursing, Faculty of Health fatin, and plasminogen activator inhibitor-1 or PAI-1) and an anti-inflammatory and Social Sciences, The Hong Kong adipokine (adiponectin). A total of 97 Hong Kong Chinese individuals aged Polytechnic University, Kowloon, Hong 57.6 ± 9.1 years with MetS and high-normal blood pressure were randomly assigned Kong, China 4 to control (n = 45) and yoga groups (n = 52). Participants in the control group were Department of Rehabilitation Sciences, Faculty of Health and Social not given any intervention but were contacted monthly to monitor their health status. Sciences, The Hong Kong Polytechnic Participants in the yoga group underwent a yoga training program with three 1-hour University, Kowloon, Hong Kong, China yoga sessions weekly for 1 year. The participants’ sera were harvested and assessed Correspondence for adipokines. Generalized estimating equation (GEE) was used to examine the in- Parco M. Siu, School of Public Health, The teraction effect between 1-year time (pre vs post), and intervention (control vs yoga). University of Hong Kong, Pokfulam, Hong Kong, China. GEE analyses revealed significant interaction effects between 1-year time and yoga Email: [email protected] intervention for the decreases in leptin and chemerin and the increase in adiponectin Funding information concentration in the sera examined. These results demonstrated that 1-year yoga Hong Kong Research Grants Council Hong training decreased proinflammatory adipokines and increased anti-inflammatory adi- Kong Ph.D. Fellowship Scheme, Grant/ Award Number: RTVX PF13-11753; Hong pokine in adults with MetS and high-normal blood pressure. These findings support Kong Polytechnic University Research the beneficial role of yoga in managing MetS by favorably modulating adipokines. Fund, Grant/Award Number: 1-ZE17; The University of Hong Kong Seed Fund for KEYWORDS Basic Research adipokine, high blood pressure, hypertension, metabolic syndrome, mind-body exercise

1 | INTRODUCTION might be another chief contributor to MetS as hypertension increases the risk for obesity and insulin resistance.2,3 Metabolic syndrome (MetS) is a clinically significant predic- Approximately 65%-75% of hypertensive individuals are tor of all-cause and cardiovascular mortality. MetS represents obese, and 50% of hypertensive individuals are insulin- a cluster of metabolic abnormalities including central obe- resistant.4 Notably, it has been shown that the prevalence of sity, high blood pressure, dyslipidemia, hypertriglyceridemia, elevated blood pressure or hypertension among people with and hyperglycemia. Central obesity and insulin resistance MetS could be as high as 85%.3 Thus, it has been proposed are considered important underlying contributors to MetS.1 that blood pressure control might be an important strategy in Furthermore, some researchers believe that hypertension reducing the risk of MetS in healthy individuals.

Scand J Med Sci Sports. 2018;1–9. wileyonlinelibrary.com/journal/sms © 2017 John Wiley & Sons A/S. | 1 Published by John Wiley & Sons Ltd 2 | SUPRIYA et al. Lifestyle modification has been suggested to be the key- of proinflammatory adipokines and increasing anti- stone for successful management of MetS.5,6 Yoga is a blend inflammatory adipokines in adults with MetS and high- of physical exercise, controlled breathing, and relaxation prac- normal blood pressure. tice. Hatha yoga, a commonly practised yoga stream, consists of asana (control of postures) and pranayama (manipulation of respiration). Yoga appears to have an antihypertensive ef- 2 | METHODS fect as well as a positive impact on self-rated quality of life. Improvements of MetS risk factors in middle-aged and older 2.1 | Study design and subject recruitment adults have been demonstrated to be associated with yoga in- This study was a follow-up to our previous randomized tervention7. One-year yoga training was shown to exert ben- controlled trial in which Chinese participants aged between eficial effect on reducing abdominal obesity and tended to 30 and 80 years who were diagnosed with MetS accord- decrease blood pressure in MetS people.7 Moreover, a short- ing to the diagnostic guidelines of the National Cholesterol term intensive yoga program (90 minutes/day for 15 consec- Education Program (NCEP) Adult Treatment Panel (ATP utive days) has also been demonstrated to cause favorable III) criteria underwent a 1-year yoga intervention program changes in body mass index, waist and hip circumference, in Hong Kong. Individuals with MetS were defined as total cholesterol, postural stability, and handgrip strength.8 having three or more of the following characteristics: (a) Indeed, yoga exercise has been shown to decrease stress, central obesity (waist circumference ≥ 90 cm for Asian reduce depression and anxiety, and increase perceived self- males or ≥ 80 cm for Asian females); (b) elevated blood efficacy in healthy individuals. The reduction in stress has glucose (fasting glucose level ≥ 5.5 mmol/L); (c) elevated been proposed as one of the potential underlying mechanisms blood pressure (systolic pressure ≥ 130 mm Hg or dias- explaining the benefits of yoga exercise.9 Intriguingly, a tolic pressure ≥ 85 mm Hg); (d) elevated plasma triglyc- cross-sectional study comparing the stress hormones between erides (triglyceride level ≥ 1.7 mmol/L); and (e) a low novice and expert yoga practitioners demonstrated that leptin level of high-density lipoprotein cholesterol (HDL-C; level was lowered and the ratio of adiponectin-to- leptin was dou- ≤ 1.03 mmol/L for males or ≤ 1.3 mmol/L for females). bled in experts when compared to novice yoga practitioners.9 Participants were randomly allocated into groups using a An epidemiological link between adiposity and hyperten- computer program. sion has been illustrated. Adipose tissue is a heterogeneous Participants having symptomatic heart or lung disease, organ comprised of subcutaneous and visceral adipose tis- pulmonary illness, severe rheumatoid arthritis or osteoarthri- sue. The incidence of hypertension has been reported to tis, dementia or mental disorder, previous stroke, severe car- be strongly associated with increased visceral adiposity.10 diovascular illness, major orthopedic problems in the lower Compared to subcutaneous adipose tissue, visceral fat is more back, neuromusculo-skeletal illness, and pelvis or lower ex- sensitive to lipolysis and secretes higher amounts of inflam- tremities were excluded. Participants who were on drug ther- matory cytokines such as PAI-1,11 visfatin,12 and chemerin.13 apy treating metabolic abnormalities, regular tobacco users, In addition to visceral adipokines, subcutaneous adipokines wheelchair users, immobile, with physical conditions not have been correlated with hypertension. Subcutaneous ad- appropriate for yoga exercise were excluded. Additionally, ipose depot secretions of leptin and adiponectin might be participants who exercised at moderate-to-vigorous inten- useful in the prediction of hypertension.14 The progressive sity at least 30 minutes per session regularly (3 or more interaction between proinflammatory and anti-inflammatory days a week) were also excluded. All the experimental pro- adipokines is commonly thought to play a significant role in cedures received human research ethics approval from The the developmental process of systemic metabolic abnormali- Hong Kong Polytechnic University (ethics approval number: ties. Therefore, the understanding of the equilibrium and bal- HSEARS20090820001 and HSEARS20160810001).7 ance of adipokines (ie, pro- vs anti-inflammatory adipokines) In this study, we specifically selected 97 blood samples of in response to lifestyle components such as physical exercise participants (control n = 45, yoga n = 52) who had MetS spe- are critically needed for the new development of regimens to cifically with high-normal blood pressure (systolic pressure combat MetS and other metabolic disorders. ≥ 130 mm Hg or diastolic pressure ≥ 85 mm Hg) from the Yoga reduces MetS risk factors15 as well as inflam- pool of 182 archived blood samples from our previous study. matory adipokines.16,17 Our previous study indicated that The samples from control and yoga intervention group were participants with MetS showed a significant decrease in selected from two time points: Pre (baseline measurement at waist circumference and a decreasing trend in blood pres- the beginning of the study) and Post (the measurement upon sure (P = .067) with moderate effect size after 1-year of accomplishment of the 1-year experimental period). Attrition yoga intervention.7 Therefore, we hypothesized that yoga rate in the study was 4.4% as some participants quitted the training would induce a favorable modulation of the ad- study due to personal reasons and some never showed up ipokine profile by reducing the circulatory abundance after the recruitment. SUPRIYA et al. | 3 2.2 | Yoga intervention 2.3 | Determination of MetS risk factors Participants in the control group were not given any in- Participants were assessed by trained research personnel tervention but were contacted monthly to monitor their for MetS diagnostic parameters including blood pressure, health status. Participants in the yoga group attended waist circumference, fasting glucose, triglycerides, and three yoga sessions weekly for 1 year. Each 60-min ses- HDL-C. The blood pressure measurement was performed sion consisted of a 10-min warm-up, 40 minutes of hatha on the right arm of the subject after a 5-min rest in a sit- yoga practice, and a 10-min cool-down that consisted of ting position. Using an appropriate-sized cuff, systolic and a breathing and relaxation exercise.7 Yoga classes were diastolic blood pressures were measured by an electronic conducted in a small group (~10 participants) by certified blood pressure monitor (Accutorr Plus, Datascope) over yoga instructors. All participants were requested to adhere the brachial artery region with the arm supported at heart to their usual daily dietary intake and physical activities level. Waist circumference was measured on the bare skin, throughout the one-year experimental period. As an incen- midway between the lowest rib and the superior border of tive, participants were offered a supermarket coupon upon the iliac crest, using an inelastic measuring tape. Venous completion of the study. Participants in the yoga group blood samples were harvested by certified phlebotomists who attended less than 70% of the classes were excluded.7 after participants fasted overnight. Blood glucose, triglyc- The training protocol of the yoga exercise program is erides, and HDL-C concentrations were measured by an shown in Table 1. accredited medical laboratory using commercial test kit

TABLE 1 The yoga postures (in both Sanskrit name of English name of Sanskrit name of English name of Sanskrit and English) practised in routine asana asana asana asana training protocol for 1-year yoga intervention group Marjaryasana to Cat to cow stretch Balasana Child pose Bitilasana Adho muha Downward dog Setu bandhasana Bridge pose svanasana Utthitaashwa High lunge Supta Reclining big toe sanchalanasana. padangusthasana pose Uttanasana Standing forward Ananda balsana Happy baby pose bend Spinal twist Matsyendrasana Virasana Hero pose Uradva hastasana Upward salute Padangusthasana Finger and toe weaving Ukatassanna Chair pose Centering In cross-legged position Virabhadrasana Warrior pose Paripurna navasana Knees bend version of boat pose Utthita parsva Side angle pose Vajrasana Thunderbolt pose konasana Utthita trikonasana Extended triangle Sukhasana). Easy pose pose Vrksasana Tree pose Shavasana Corpse pose Malasana Garland pose Eka pada bhekasana 1-leg frog pose Eka pada One-legged king Sputa baddha Lying down bound rajakapotasana pigeon pose konasana angle pose Salambhasana Locust pose Uttitha hasta Extended big toe padangustasana pose Dandasana Staff pose Sputa padangusthana Big toe lying down pose Baddha konasana Bound angle pose Padangusthasana Big toe pose Agnistambhasana Fire log pose Salabasana Locust pose Gomukhasana Cow face pose Tadasana Mountain pose 4 | SUPRIYA et al. methods and an automatic clinical chemistry analyzer international physical activity questionnaire or IPAQ), and (Architect CI8200, Abbott Diagnostics, USA).7 Systolic adipokines at the baseline assessment between control and blood pressure, diastolic blood pressure, fasting plasma yoga groups (Table 2). Our analysis revealed that among all glucose, waist circumference, HDL-C, and triglycerides the other MetS risk factors that were measured, the mean were examined at baseline and at the end of the 1-year ex- change (ie, post-pre) in waist circumference was significantly perimental period. Furthermore, the detailed explanations lower in the yoga group compared to the control group (−3.6 about the methods used for the assessment of MetS risk vs −1.4, P = .029) (Figure 1). The mean waist circumference factors are described in our previous publication.7 value was reduced by 4% in the yoga group and 2% in control group (Figure 2F). Further analysis revealed that there was no significant in- 2.4 | Measurement of adipokines teraction effect between time and intervention for diastolic Commercially available enzyme-linked immunosorbent assay blood pressure, systolic blood pressure, high-density lipopro- (ELISA) kits (Visfatin from BioVision; PAI-1 and chemerin tein, triglycerides, fasting glucose, and waist circumference from R&D; leptin and adiponectin from Thermo Fisher in our examined MetS participants with high-normal blood Scientific, USA) were used to examine the concentrations of pressure (Figure 2). Of note, we also found no significant in- adipokines in the serum samples according to the manufac- teraction effect between time and intervention on MetS risk turer’s instructions. The coefficients of variability (CV) for the factors in MetS participants with high-normal blood pressure kit assays are as follows: visfatin (intra-assay: 4.4%-8%, interas- after adjusting for the age as a covariate. The main effect of say: 8.2%), PAI-1 (intra-assay: 6.8%, interassay: 7%), chemerin time was observed for systolic blood pressure (Wald Chi- (intra-assay: 3.9%, interassay: 7.3%), leptin (intra-assay: 3.9%, square test= 12.4, P < .001), diastolic blood pressure (Wald interassay: 5.3%), and adiponectin (intra-assay: 3.8%, interas- Chi-square test= 6.3, P = .012), and waist circumference say: 5.5%). Measurements were performed in duplicates or trip- (Wald Chi-square test= 4.4, P = .037) (Figure 2A,B and F). licates by a single observer to minimize the observer variation. 3.2 | Anti- and proinflammatory adipokines 2.5 | Data analyses Our results revealed significant differences in the mean Data are expressed as the means ± standard deviation. The gen- value of change (ie, post-pre) in adiponectin (−1.0 vs 1.3, eralized estimating equation (GEE) was adopted to examine the P < .001), PAI-1 (0.9 vs 0.4, P = .03), chemerin (46.3 vs interaction effect between 1-year time and the intervention, the −32.8, P < .001), and leptin (1.9 vs −6.7, P < .001) in the main effect of time, and the main effect of intervention on adi- control vs. yoga groups (Figure 3A-D). The mean value pokines and MetS risk factors. GEE was also used to examine of adiponectin levels in the yoga group was increased by the interaction effect between 1-year time and the yoga interven- 20.1% compared to a decrease of 15.5% in the control group tion on MetS risk factors after adjusting the age as a covariate. (Figure 4A). Moreover, the mean values of leptin, PAI-1, Normality of the data was verified by the Shapiro-Wilk test. The and chemerin were significantly decreased (26.5%, 6.5%, and Mann-Whitney U test was performed to examine the baseline 14.3%, respectively) in the yoga group compared to increases differences in MetS risk factors, age, sex and the changes (post- in each variable (9%, 13.5%, and 21%, respectively) in the pre) in the MetS risk factors and adipokines between control and control group (Figure 4B,C and D). yoga groups. The Chi-square test was performed to examine the Our further analysis revealed the significant interaction baseline differences in the categorical data. All statistical analy- effects between time and intervention for adiponectin (Wald ses were performed using the Statistical Package for the Social Chi-square test= 16.2, P < .001), leptin (Wald Chi-square Sciences (SPSS) version 22 for Windows. Statistical signifi- test= 9.4, P = .002), and chemerin (Wald Chi-square test= cance was indicated by P < 0.05. Our power analyses indicated 11.6, P = .001) (Figure 4A,B and D). The main effect of that the statistical power was >80% for most of the outcome yoga intervention was found for PAI-1 (Wald Chi-square measures performed in this study including adiponectin, leptin, test= 5.9, P = .015) (Figure 4C). However, the main effect of chemerin, visfatin, diastolic blood pressure, and systolic blood time was observed for visfatin (Wald Chi-square test= 11.78, pressure. P = .001) (Figure 4E).

3 RESULTS | 4 | DISCUSSION

3.1 | MetS risk factors MetS is a serious public health concern due to its intimate No significant differences were observed in the MetS risk link to the pathogenesis of diabetes mellitus, stroke, and factors, habitual physical activity level (as assessed by cardiovascular diseases. In 2010-2012, the prevalence rate SUPRIYA et al. | 5 TABLE 2 Baseline characteristics of Control group Yoga group metabolic syndrome risk factors, IPAQ (n = 45) (n = 52) P-value activity and sitting, and adipokines in control and yoga groups Gender 17 M, 28 F 17 M, 35 F .60 Age (yrs) 56.5 ± 8.6 58.5 ± 9.5 .26 Diastolic blood pressure (mm Hg) 85.8 ± 8.8 84.5 ± 7.8 .35 Systolic blood pressure (mm Hg) 141.7 ± 13.8 140.3 ± 13.5 .35 Waist circumference (cm) 89.8 ± 7.1 90.4 ± 9.2 .78 Fasting glucose (mmol/L) 5.56 ± 0.9 5.58 ± 0.5 .23 Blood triglycerides (mmol/L) 2.1 ± 1.0 1.9 ± 0.9 .33 Blood high density lipoprotein-C 1.3 ± 0.3 1.2 ± 0.3 .52 (mmol/L) IPAQ activity (min/week) 3888.78 ± 4204.1 2593.66 ± 2232.3 .16 IPAQ sitting (min/wk) 2532.78 ± 1774.1 2306.75 ± 1500.3 .99 Adiponectin (ng/mL) 6484 ± 1803 6409 ± 1753 .88 Plasminogen activator inhibitor-1 6.4 ± 2.6 6.0 ± 2.6 .28 (ng/mL) Visfatin (ng/mL) 3.5 ± 2.9 3.5 ± 2.0 .18 Chemerin (ng/mL) 221.4 ± 70.7 230.1 ± 90.4 .60 Leptin (ng/mL) 22.2 ± 9.8 25.4 ± 11.5 .18

circulatory anti-inflammatory adipokine (adiponectin) and decreases proinflammatory adipokines (leptin, chemerin, and PAI-1) in MetS participants with high-normal blood pressure. These novel results support the beneficial com- plementary role of yoga exercise in the management of MetS by illustrating the favorable modulating effects of yoga training on blood adipokines. Reduction in waist circumference and blood pressure has been shown to be positive health consequences of reg- 7,19 FIGURE 1 Change in waist circumference in control and yoga ular yoga training. Waist circumference and visceral fat groups. The box plot represents the change (ie, post-pre) in waist were decreased after 16 weeks of yoga training compared circumference after yoga training in subjects with MetS and high- to a control group of healthy post-menopausal women aged 19 normal blood pressure. Statistical significance was set at P < .05 54.5 ± 2.8 years. Overweight/obese women and breast cancer survivors have also been shown to reduce waist circumference after receiving 6 months of yoga training when of MetS in Hong Kong was ~27% according to the NCEP compared to breast cancer survivors who did not receive yoga ATP III criteria.7 Central obesity and insulin resistance intervention.20 Another study demonstrated that blood pres- have been proposed as the prominent underlying contribu- sure was significantly reduced by yoga exercise intervention tors to MetS. Remarkably, as high as 85% of MetS individ- in patients with mild hypertension.21 Consistently, our previ- uals have been shown to have elevated blood pressure or ous investigation also demonstrated that 1-year yoga training hypertension.3 Individuals with both MetS and hyperten- decreased waist circumference and tended to reduce systolic sion are indeed considered to be significantly challenged blood pressure in middle-aged and older adults with MetS and at risk for additional morbidities.18 Adipocytes syn- compared to the control group who did not receive yoga in- thesize and release adipokines such as adiponectin, leptin, tervention.7 Our results are in accordance with the previous angiotensin, perivascular relaxation factors, and resistin, findings that the average waist circumference was signifi- which are all linked with blood pressure control. As adi- cantly decreased; however, both systolic and diastolic blood pokines are considered regulators of MetS, the equilibrium pressures were not decreased in participants with yoga inter- and balance of adipokines become an important topic to be vention compared to the control participants with MetS and explored in studies of obesity, hypertension, and MetS. Our high-normal blood pressure. This study further explored the present findings reveal that 1-year yoga training increases a effect of yoga on the specific subject group with MetS and 6 | SUPRIYA et al.

FIGURE 2 Cardiometabolic risk factors in control and yoga groups. Line graphs represent the changes in systolic blood pressure (A), diastolic blood pressure (B), high-density lipoprotein cholesterol (C), triglycerides (D), fasting glucose (E), and waist circumference (F) before (Pre) and after (Post) the 1-year experimental period in MetS subjects with high-normal blood pressure in control (n = 45) and yoga groups (n = 52). Statistical significance was set at P < .05. Data are expressed as the means ± standard deviation high-normal blood pressure by investigating the interaction including MCP-1, IL-8, and IP-10 were significantly higher effect between yoga and the 1-year time period. Our results in participants who developed T2D during a follow-up of indicated that there was no interaction effect between yoga 10 years compared with those who did not develop T2D.23 and the 1-year time period for any of the five risk factors of An aerobic exercise (225 min/wk) intervention conducted on MetS in our examined participants with high-normal blood post-menopausal inactive women resulted in decreases in in- pressure. In accordance with our previous study assumptions sulin resistance markers (leptin, adiponectin/leptin ratio, in- that the effects of yoga exercise on systolic blood pressure sulin), whereas changes in glucose (one of the risk factors for might be dependent on the quantity of the intervention and/or MetS) were not evident.24 Another study by the same group subject compliance to the intervention,7 we again suggested suggested that adipokines and systemic inflammation may be that extra attention should be given to MetS participants associated with the risk of breast cancer in post-menopausal with high-normal blood pressure. The controversial results women independent of body mass index.25 They concluded might be explained by the complexities involved in defining that after performing long-term aerobic exercise, previously MetS. An equal number of MetS risk factors might not in- inactive post-menopausal women showed changes in insulin, dicate that the participants shared the same characteristics leptin, and adiponectin/leptin, which might reduce the risk and cardiometabolic risk factor profile. Indeed, the specific of post-menopausal breast cancer.24 Numerous studies sup- outcomes/consequences of MetS are difficult to evaluate port the idea that hypertensive patients with MetS will show without a solid definition and common criteria for diagnosis. early signs of end-organ damage, which are recognized as Nonetheless, our results support the notion that “MetS in hy- significant independent predictors of adverse cardiovascular pertension is an unholy alliance.”18 outcomes compared to those without MetS.26 Therefore, in- Evidence indicates that biomarkers might be valuable in dividuals with high-normal blood pressure and MetS should diagnosing and estimating the disease risk for a population receive special attention. and managing many pathological states, especially when Researchers suggested that MetS identification should be clinical signs or obvious anatomic abnormalities are absent emphasized when treating patients with hypertension.27,28 In or not evident.22 For example, insulin resistance is one of the this study, adipokines were observed to be favorably regulated major risk factors of type 2 diabetes (T2D). Markers for indi- after yoga intervention in MetS subjects with high-normal cating insulin resistance might be useful for prevention of car- blood pressure. These results proposed that an adipokine diovascular disease, all-cause mortality, and T2D. Increased panel as a circulatory biomarker might be useful for identi- concentrations of interleukin-8 (IL-8), monocyte chemotactic fying the protective outcomes of interventions, especially in protein-1 (MCP-1), and interferon γ-induced protein (IP-10) worsening metabolic conditions in which changes in clinical have been associated with the incidence of T2D by hazard outcomes are not obvious. Biomarkers aid in the diagnosis ratio risk assessment. One study suggested that chemokines and management of many pathological states when there SUPRIYA et al. | 7

FIGURE 3 Changes in adipokines in control and yoga groups. Box plots represent the changes (ie, post-pre) in adipokines including adiponectin (A), plasminogen activator inhibitor-1 (B), chemerin (C), and leptin (D) after yoga training in subjects with MetS and high-normal blood pressure. Statistical significance was set at P < .05 are no obvious clinical signs or anatomic abnormalities.13 Yoga exercise has been shown to alleviate inflammatory Nonetheless, each adipokine has a particular role in maintain- signalling by downregulating the regulatory molecule that ing the delicate equilibrium between the pathophysiological favors the proinflammatory microenvironment,31 namely, effect and protective impact. Although numerous effects of the nuclear factor kappa-light- chain- enhancer of activated adipocytokines have been reported in recent studies, further B cells (NF-κB).32 Consistent with the role of NF-κB, the investigation of their signalling pathways is still needed to downregulation of the regulatory molecules for the proin- understand how they are eventually integrated. flammatory microenvironment reasonably explains the The regular practice of yoga exercise has been demon- principal behind the first mechanism. The second mecha- strated to be effective in reducing stress and improving nism is attributed to the reactivation of the parasympathetic physical and psychologic health. Yoga exercise has also nervous system by consciously manipulating the breath been proposed to reduce oxidative stress by at least two rhythm (ie, slow breathing and a long exhalation) during mechanisms.29,30 The first mechanism is via the suppres- yoga practice.25 The activities of adenosine monophosphate- sion of the overactivated sympathoadrenal system and the activated protein kinase (AMPK) in peripheral tissues and hypothalamic-pituitary- adrenal (HPA) axis,29,30 which re- organs are known to be facilitated by the specific regulation duces the proinflammatory responses by decreasing the lev- of the sympathetic and parasympathetic nervous systems.33 els of stress hormones such as cortisol and epinephrine.29,30 Intriguingly, AMPK is a regulatory molecule that favors

FIGURE 4 Adipokines in control and yoga groups. Line graphs represent the concentrations of leptin (A), plasminogen activator inhibitor-1 (B), chemerin (C), visfatin (D), and adiponectin (E) before (Pre) and after (Post) the 1-year experimental period in MetS subjects with high-normal blood pressure in control (n = 45) and yoga groups (n = 52). Statistical significance was set at P < .05. Data are expressed as the means ± standard deviation 8 | SUPRIYA et al. the anti-inflammatory microenvironment. AMPK functions PF13-11753), The Hong Kong Polytechnic University to mediate fat oxidation, reduce circulating fatty acids and Research Fund (1-ZE17), and The University of Hong Kong triacylglycerol, and increase glucose transport in muscle. Seed Fund for Basic Research. In mammals, AMPK has been demonstrated to contribute to glucose homeostasis, appetite regulation, and exercise 34 CONFLICT OF INTEREST adaptation. Thus, the upregulation of anti-inflammatory responses by increasing fat oxidation, reducing circulatory All authors declare no conflict of interest. fatty acids, and promoting insulin sensitivity through the AMPK pathway sensibly contributes to the principal behind AUTHOR CONTRIBUTIONS the second mechanism. Nevertheless, the precise underlying mechanisms that explain how yoga practice causes the R.S. contributed to design, conduct/data collection, analysis observed alterations of circulatory adipokines are unclear, of the paper, and writing of the paper. A.P.Y. contributed and this topic warrants additional research to fully under- to data collection. P.H.L. contributed to statistical analyses. stand the relationship between yoga exercise training and the C.W.L., L.W.C., and B.Y.Y. contributed to design and analy- adipokine profile. Provided that MetS is a condition that is sis of the paper. K.K.C. and S.Y.Y. contributed to analysis of characterized by chronic low-grade inflammation, it is ratio- the paper. P.M.S. contributed to the design, analysis of the nal that an equilibrium between the anti-inflammatory and paper, and writing of the paper. proinflammatory microenvironments plays a critical role in preventing the development of MetS. ORCID We aimed to provide an estimate of the true efficacy of the intervention, that is, among those who completed the treat- Paul H. Lee http://orcid.org/0000-0002-5729-6450 ment as planned (per protocol analysis). Nonetheless, the Parco M. Siu http://orcid.org/0000-0002-3548-5058 convenience sampling with restricted inclusion criteria and the use of per protocol analysis in our study design might have limited the study generalizability and exaggerated the REFERENCES treatment effect. Future research with the inclusion of both 1. Wahba IM, Mak RH. 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