Polyglycolic acid sutures embedded in abdominal acupoints for treatment of simple obesity in adults: a randomized control trial

Obesity elicited by the interaction of genetic and environmental factors is a culprit of many metabolic dysfunctions including insulin resistance, dyslipidemia, hypertension and even certain cancers [1]. Simple obesity refers to the type of obesity which associates with unhealthy lifestyles while having no other complications, e.g. diabetes mellitus or polycystic ovary syndrome [2, 3], and it is characterized by expansion of fat mass and adipocyte size, as well as lesser extent adipocyte proliferation. An epidemiological survey on 19.2 million adult participants (9.9 million men and 9.3 million women) in 186 countries suggests that the prevalence of obesity markedly ascends from 3.2% in 1975 to 10.8% in 2014 in men and from 6.4% in 1975 to 14.9% in 2014 in women. If the trends continue, by 2025 global obese ratio will reach 18% in men and surpass 21% in women [4]. According to the World Health Organization (WHO) report in 2010, at least 3.4 million adults died from overweight or obesity-related diseases each year [5]. Therefore, adiposity has become a predominant public health concern.

Although pathological mechanisms of simple obesity are complex, present consensus are metabolic regulation, neurohormonal and haemodynamic dysfunctions resulted in inflammation, lipotoxicity, apoptosis, oxidative stress, autophagy alterations and disorders of energy homeostasis and cellular metabolism [6]. Excessive adipose tissues infiltrated by various immune cells play a critical role in the production of chronic low-grade inflammation. It contributes to the onset of type 2 diabetes mellitus (T2DM) and cardiovascular complications [7]. Due to harmful features of simple obesity for health, many intervention strategies emerge as weight loss requirement. The most conventional way of weight control is lifestyle modification, which includes diet, exercise, and behavior therapy [8]. Obese populations are required to habituate regular physical activity and exercise, restrict high carbohydrate and fat intakes, and self-monitor food intake, physical activity and body weight. Although some people fail to maintain the lifestyle modification followed by recovering previous weight, lifestyle-treated persons still display low incidence of T2DM, showing beneficial effect on long-term health [9]. Additionally, studies also indicate the change of diet and/or exercise, as well as cognitive behavioral therapy for obese individuals do not produce distinct or sustainable weight loss. It is necessary to develop anti-obesity drugs by decreasing the consumption or absorption of food, and/or increasing energy expenditure [10]. However, due to unacceptable side effects, some new anti-obesity drugs have to be withdrawn. Traditional pharmacological monotherapies for obesity usually evoke counter-regulation, so new anti-obesity drugs not only possess sustained efficacy of weight loss, but also improve comorbidities by targeting multi-biological mechanisms in future. As an invasive approach, bariatric surgery quickly and effectively decreases adipose tissue for weight loss, but it is easy to elevate perioperative mortality and surgical complications. Thereby, operative treatment is regarded as only suitable for the treatment of morbidly obese [11]. Until now, researchers are still looked for satisfied therapy for anti-obesity.

From the view of Chinese medicine theory, the etiology of obesity mainly associates with improper lifestyle resulted in the production of Phlegm-damp due to spleen Qi deficiency. Accumulated Phlegm-damp subsequently transforms to stagnation heat, phlegm heat, dampness heat and stasis heat, which leads to the status of chronic inflammation in simple obesity [12]. Chinese medicine has the characteristic of holism, so systemic effects of Chinese materia medica or acupuncture contribute to regulation of obesity body. However, due to unclear compositions and vague mechanisms for Chinese materia medica, it hinders their wide application. For example, aristolochic acids and similar compounds from Aristolochia and related plants are mutagenesis attribution to liver cancers in Asia population [13]. While acupuncture is relatively safe therapeutic method and has been widely used in clinical practice [14]. Numerous clinical data have demonstrated that acupuncture for simple obesity is an effective method by regulation of endocrine system, promotion of digestion, attenuation of oxidative stress and modulation of relevant metabolic molecules [6, 15]. Acupoint catgut embedding (ACE) is a special acupuncture technology, whose characteristics including acupoint, needle and catgut are available to exert more comprehensive therapeutic efficacy compared with acupuncture alone. A meta-analysis of 43 trials within 3520 patients shows that ACE effectively reduces body weight, hip circumference (HC) and waist circumference (WC), and the efficacies are greater than/or equal to other kinds of acupuncture and drugs and nondrug therapy. Even in some sense, ACE may be more advantageous to obese treatment [16]. However, it is still deficient in high-quality clinical research evidence and evaluation of ACE safety for treatment of simple obesity [17]. In present study, polyglycolic acid sutures, as a novel biodegradable material, are used to embed in abdominal acupoints of obese populations instead of common catgut. Subsequently, we assess the efficacy and disclose corresponding mechanisms of the polyglycolic acid sutures embedding therapy (PASET) on simple obesity.

In present study, we use polyglycolic acid sutures instead of traditional catgut to embed in abdominal acupoints for simple obesity treatment. It shows that the novel therapeutic technology significantly reduces body weight, BMI, HC, WC, WHR, WtHR and the thickness of abdominal subcutaneous fat tissue, improves evaluated scores of physical function, self-esteem, public distress and sexual life, decreases blood pressure, glycemia, LDL, uric acid and increases HDL, as well as down-regulates the levels of TNF-α and IL-1β in obese persons. The efficacies of PASET are superior to lifestyle modification.

The increasing prevalence of overweight and obese adults has become a public concern problem. Obesity not only causes, or aggravates some pathological progress, such as cerebral-cardiovascular disease, diabetes, gallstones and musculoskeletal diseases, but also influence quality of life including depression, anxiety, stress, lower self-esteem and sexual dysfunction [25]. IWQOL-Lite is a self-evaluated report consisting of a total score and scores on each of five scales, which exhibits strong psychometric properties and clinically sensitive brief measure of quality of life in obese persons [20, 26]. In current study, 51 participators completed the IWQOL-Lite, and PASET group exerts main therapeutic effects on amelioration of quality of life by enhancing total scores and scores of four areas in physical function, self-esteem, sexual life and public distress after treatment. However, control group fails to suggest advantageous efficacy on improvement of quality of life using lifestyle modification at the end of the treatment. Due to obese persons living in their houses, it is difficult to accurately assess the food intake although hypocaloric diets menu had been established, as well as if the intensity and time of exercise were accordance with the physical requirement. The limitations should be avoided by effective monitoring methods followed by trial.

Long-term abdominal obesity causes alterations of hormonal, inflammatory and endothelial level, which contribute to the hypertensive state [27]. Excessive adipose tissue release free fatty acid (FFA) resulted in obesity-related dyslipidemia. The enhanced FFA delivers into live and produces hypertriglyceridemia as well as low concentration of HDL and high concentration of LDL [28]. LDL cholesterol has been crucial actual atherogenic risk, since a high concentration of small, dense LDL cholesterol closely associates with a high prevalence of cardiovascular disease [29]. Our study indicates that PASET either lows values of diastolic and systolic pressures in obese persons, or enhances HDL concentration and decreases LDL level. Although both of PASET and control groups show slight decline of triglyceride concentration, there is no statistical significance after treatment. Nevertheless, the beneficial efficacy of PASET on dyslipidemia and blood pressure contributes to reduction of cerebral-cardiovascular disease risk factors. In addition, we also find PASET notably reduces uric acid level. Whether the elevated serum uric acid is casual or a consequence of obesity confuse researchers for a long time. Zheng and colleagues demonstrated that high serum uric acid levels increased the risk of obesity by a longitudinal 4411 obese subjects clinical trial [30]. Therefore, PASET decreases the level of serum uric acid is benefit to further attenuation of obese risk.

Evidence suggests that chronic low-grade inflammation in adipose tissue plays a predominant role in the development of obesity-related metabolic dysfunction [31]. In the obese state, necrotic adipocyte recruits macrophages to secret pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-6, MCP-1, which potentially arouses obesity-related insulin resistance [28]. In order to interrupt the pathological progress of T2DM onset in obese persons, anti-inflammatory response is a necessary therapeutic approach [32]. Our study showed that PASET distinctly reduced the concentrations of TNF-α and IL-1β, two powerful pro-inflammatory cytokines, as well as decreased IL-6, MCP-1 levels although there was no statistical difference between them. It suggest PASET may regulate macrophage polarization from pro-inflammatory phenotypic to anti-inflammatory status. Interestingly, we found IL-18 level slightly ascends after PASET. Some studies evidence that circulating increased IL-18 associates with obese subjects and metabolic syndrome [33, 34]. However, knockout mice deficient in IL-18 or IL-18 receptor cause hyperphagia, obesity and insulin resistance, and it is worth reassessing the role of IL-18 in the pathogenesis of obesity and insulin resistance [28, 35]. We hypothesize the change of IL-18 level in our study may contribute to the energy expenditure via PASET for obese persons, because Ye and McGuinness think inflammation during obesity is not all bad and promoted IL-18 may exerts a protective effect on limiting adiposity [36]. Of course, precision mechanism needs to be investigated in next experiment.

In the evaluation of safety on simple obesity using PASET, our results indicate the therapeutic technology is relative safe. Only one participator subjected to erythematous subcutaneous nodule on embedding site of abdomen, and the nodule and hyperpigmentation eventually disappeared after 3.5 months. Hsu and colleagues reported that erythematous swelling and nodules appeared in the acupuncture points on abdomen of a 27-year-old woman who received the acupuncture point catgut embedding treatment, and the complications disappeared 6 months later [37]. It suggests the complications of PASET can quickly attenuate compared with those of catgut embedding treatment. In addition, participators also can tolerate the pain feeling during the process of PASET and no one withdraws the trial due to pain or discomfort.

Based on the advantageous actions on ameliorations of quality of life, metabolic profile and inflammatory response by PASET, it contributes to weight loss, which embodies the decreases of weight, BMI, HC, WC, WHR, WtHR as well as abdominal subcutaneous fat thickness by scanning of B-model ultrasound. Therefore, we think PASET is an effective therapeutic approach in the treatment of simple obesity.