Prevention and Treatment of Obesity Type 2 Diabetes Mellitus by Traditional Chinese Medicine Through AMPK Signaling Pathway： A Review / 中国实验方剂学杂志

Obesity type 2 diabetes mellitus （T2DM） strengthens insulin resistance （IR） and metabolic abnormalities and significantly increases the risk of heart disease， cancer， and other diseases， and it is characterized by IR and malnutrition. As a metabolic regulation center， adenosine phosphate activated protein kinase （AMPK） mainly responds to the changes in intracellular serine/threonine kinase adenosine monophosphate （AMP） levels. After its activation， AMPK converts the cell metabolism mode from synthesis to decomposition to improve energy metabolism and acts on pathological conditions such as inflammation， ischemia， obesity， and aging. In recent years， a large number of studies have found that AMPK is an important target for the treatment of obesity T2DM. Traditional Chinese medicine（TCM） monomers/extracts and TCM formulas mainly affect the mammalian target of rapamycin （mTOR）， recombinant sirtuin 1 （SIRT1）， nuclear factor erythroid 2-related factor 2 （Nrf2）， nuclear factor kappa-B （NF-κB）， and other key signaling factors by regulating the AMPK signaling pathway， so as to achieve a variety of effects such as regulating metabolism and autophagy， reducing oxidative stress and inflammatory response， and treating obesity T2DM. It also has advantages such as multiple targets， comprehensiveness， and low toxicity. The regulation of the AMPK pathway by TCM in the prevention and treatment of obesity T2DM has become an important research direction at the present and in the future， but there is no systematic summary and induction in this field. Therefore， this article attempts to summarize the composition and regulatory mechanisms of the AMPK signaling pathway in affecting obesity. It provides a review of the current research status of TCM in regulating the AMPK signaling pathway for the prevention and treatment of obesity T2DM， so as to provide a reference for the diagnosis and treatment of obesity T2DM in TCM and the development of new drugs.

The gut peptide Reg3g links the small intestine microbiome to the regulation of energy balance, glucose levels, and gut function.

Changing composition of the gut microbiome is an important component of the gut adaptation to various environments, which have been implicated in various metabolic diseases including obesity and type 2 diabetes, but the mechanisms by which the microbiota influence host physiology remain contentious. Here we find that both diets high in the fermentable fiber inulin and vertical sleeve gastrectomy increase intestinal expression and circulating levels of the anti-microbial peptide Reg3g. Moreover, a number of beneficial effects of these manipulations on gut function, energy balance, and glucose regulation are absent in Reg3g knockout mice. Peripheral administration of various preparations of Reg3g improves glucose tolerance, and this effect is dependent on the putative receptor Extl3 in the pancreas. These data suggest Reg3g acts both within the lumen and as a gut hormone to link the intestinal microbiome to various aspects of host physiology that may be leveraged for novel treatment strategies.

Effects of liraglutide or lifestyle interventions combined with other antidiabetic drugs on abdominal fat distribution in people with obesity and type 2 diabetes mellitus evaluated by the energy spectrum ct: A prospective randomized controlled study.

Objective: To study the effects of liraglutide or lifestyle interventions combined with other antidiabetic drugs on glucose metabolism and abdominal fat distribution in patients with obesity and type 2 diabetes mellitus (T2DM). Methods: From April 30, 2020, to April 30, 2022, a prospective randomized controlled study was carried out at the Endocrinology Department of Beijing Hospital, the National Center of Gerontology. According to the in- and exclusion criteria and by the random table method, revisited T2DM patients were selected as the research subjects and were allocated into a Study group (taking liraglutide) and a Control group (underwent lifestyle interventions). All patients received continuous 12-weeks interventions to the endpoint, and the changes of value [Δ=(endpoint)-(baseline)] of physical measurements, blood tests, the energy spectrum CT examination results, and body composition analysis results were analyzed and compared. Results: A total of 85 people completed this study, and among them, 47 were in the Study group and 38 were in the Control group. Compared with the Control group, the changes of hemoglobin A1c (HbA1c) level (-0.78 ± 1.03% vs. -1.57 ± 2.00%, P=0.025), visceral fat area (0.91 ± 16.59 cm2 vs. -7.1 ± 10.17 cm2, P=0.011), and subcutaneous fat area of abdomen [0 (-18.75, 15.5) cm2 vs. -16.5 (-41.75, -2.25) cm2, P=0.014] were all greater in the Study group. The adverse events caused by liraglutide were mainly concentrated in the gastrointestinal system and all of them were minor adverse events. Conclusion: Liraglutide can be the drug of choice for weight management and reduction of abdominal fat distribution in patients with obesity and T2DM.

Metabolic optimization in diabetes: A hierarchial model.

Diabetes care involves a rational understanding of the complex clinical and pharmacological interactions. If we have clarity of thought in our goals and aims, it becomes much easier to plan treatment strategies. The hierarchal model of metabolic modulation and optimization represents an effort to achieve simplicity and straightforwardness in deciding aims of diabetes care, planning approaches, and choosing the right arsenal for intervention. This model lists the targets of therapy as symptomatic, glucometabolic, vasculometabolic, barometabolic and viscerometabolic optimization.

The Islet De-stress Hypothesis: A potential explanation for the gluco metabolic effects of ketogenic diet.

Ketogenic diet (KD) is an established therapy with indications which span multiple disciplines. Initial skepticism about the role of KD in diabetes and obesity has been replaced by interest in its mechanism of action. We propose that KD works by de-stressing the islet of Langerhans, and reducing its workload. This de-stress occurs at both beta and alpha cell, and suggests that the islet should be considered a single anatomic-functional unit. The Islet De-stress Hypothesis, as we term it, is based upon the Law of Endocrine Parsimony. Simply put, this states that minimal burden should be placed on any gland, including the islet of Langerhans, while managing endocrine disease.

Pre ketogenic diet counselling.

This communication describes the aims and aspects of counseling prior to start of a ketogenic diet (KD). It uses a reader-friendly bio-psycho-social format to list and structure the various components of pre ketogenic diet counseling. These include strength mapping, risk and benefit explanation, and understanding the patient's selfcare responsibilities. This simple, yet practical discussion fills a major void in current literature, which seems to have ignored patient centred counseling strategies for KD in persons with obesity and diabetes.

Multiple endocannabinoid-mediated mechanisms in the regulation of energy homeostasis in brain and peripheral tissues.

The endocannabinoid (eCB) system is widely expressed in many central and peripheral tissues, and is involved in a plethora of physiological processes. Among these, activity of the eCB system promotes energy intake and storage, which, however, under pathophysiological conditions, can favour the development of obesity and obesity-related disorders. It is proposed that eCB signalling is evolutionary beneficial for survival under periods of scarce food resources. Remarkably, eCB signalling is increased both in hunger and in overnutrition conditions, such as obesity and type-2 diabetes. This apparent paradox suggests a role of the eCB system both at initiation and at clinical endpoint of obesity. This review will focus on recent findings about the role of the eCB system controlling whole-body metabolism in mice that are genetically modified selectively in different cell types. The current data in fact support the notion that eCB signalling is not only engaged in the development but also in the maintenance of obesity, whereby specific cell types in central and peripheral tissues are key sites in regulating the entire body's energy homeostasis.

Effect of short-term energy metabolism by which sleeve gastrotomy (SG) and gastric plication (GP) alter on obesity type 2 diabetes Zucker fatty rats / 中华内分泌外科杂志

Objective To investigate the effect of sleeve gastrotomy (SG) and gastric plication (GP) on the short-term metabolism in type 2 diabetes mellitus (T2DM) Zucker fatty rats.Methods Thirty healthy male rats were randomly allocated into three groups:Sham,SG and GP groups,and devices like metabolic cage were applied to detect the metabolic changes in the third week after operation.Results The body weight of the SG and GP group decreased,but no statistical significance was found when compared with that of the Sham group.Less food consumption were found in SG (P＜0.05) and GP (P＜0.05) groups compared with that of the Sham group.In the daytime,the energy expenditure of SG group was higher than that of the sham group(P＜0.01),while in the night,the energy expenditure of both the SG (P＜0.001) and GP (P＜0.001) groups were higher than that of the Sham group.In the night,the activity level of SG (P＜0.05) and GP (P＜0.05) groups were lower than that of the Sham group,and activity level in the night was lower than that in the daytime for SG group(P＜0.05).In the daytime,the respiratory exchange rate (RER) of the SG (P＜0.001) and GP (P＜0.001) group were lower than that of the Sham group,and the night RER of GP group was higher than that in the daytime (P＜0.05).No statistical significance was found in terms of the average speed among the three groups.The average speed of the Sham (P＜0.05) and SG (P＜0.05) group in the night were faster that in the daytime.The fasting plasma glucose (FPG) of SG and GP group were improved compared with that of the Sham group.Conclusion SG and GP procedures can improve the metabolism of diabetic rats in the short term.

Visualization Analysis on Research Trends of Prevention and Treatment of Obesity Type 2 Diabetes Mellitus with TCM in Recent Two Decades / 中国中医药信息杂志

Objectives To use visualization method to analyze the relevant literature about prevention and treatment of obesity type 2 diabetes mellitus (T2DM) with TCM; To understand research hot spots and development trends of this field. Methods Computers were used to retrieve prevention and treatment of T2DM with TCM in CNKI. CiteSpaceV was used to visualize the authors, research institutes and keywords, and discussed their research hot spots, research frontiers, major research groups and trends. KNS6.6 was used to quantitatively analyzed included literature distribution characteristics, core citations, etc., and conducted visual display. Results After screening, 130 articles were included, involving 257 researchers and 6 research institutes, among which, TONG Xiao-lin, DONG Liu, ZHOU Li-bo, etc. were the main researchers. Guang'anmen Hospital of China Academy of Chinese Medical Sciences is the most important research institute, followed by Beijing University of Chinese Medicine, Changchun University of Chinese Medicine and Guangzhou University of Chinese Medicine. The main research directions included the diagnosis and treatment of obesity T2DM, acupuncture and moxibustion treatment, the mechanism of TCM intervention in inflammation. This study predicted exploration of the TCM pathogenesis of obesity T2DM and the construction of TCM clinical pathway may be the future research trends and hot spots. Conclusion Through visualization analysis, the main research directions in the field in recent 20 years, research hot spots, evolution veins and development trends can be understood quickly and intuitively, providing a basis for further research.

Health-Related Quality of Life after Bariatric Surgery and its Correlation with Glycaemic Status in Hong Kong Chinese Adults.

BACKGROUND: To evaluate health-related quality of life (HRQOL) following bariatric surgery and its correlation with different glycaemic status in Hong Kong Chinese adults. MATERIALS AND METHODS: In 2002-2008, obese Chinese adults were recruited for bariatric surgery, undergoing laparoscopic adjustable gastric banding or laparoscopic sleeve gastrectomy. Patients were invited to complete the Chinese Hong Kong Medical Outcomes Study Short-Form Health Survey (SF-36) at baseline and at 1-year post operation. RESULTS: Sixty patients (60 % female) completed baseline and 1-year follow-up HRQOL assessments. Mean age was 38 years and mean BMI was 41.6 kg/m(2). At baseline, 30.0 % of patients had diabetes and 31.7 % prediabetes. Mean absolute weight reduction 1 year after bariatric surgery was 19.8 kg. Statistically significant improvements in SF-36 scores were demonstrated in all physical domains and in three of the four psychological domains. Greater body weight reduction was associated with greater improvements in certain physical domains postoperatively. After adjusting for co-variables, abnormal glucose tolerance was associated with greater improvements in five of the eight HRQOL domains. CONCLUSIONS: Bariatric surgery resulted in significant gains in HRQOL as well as significant reductions in body weight in obese Chinese adults. This study suggests that bariatric surgery offers greater HRQOL improvements in patients with prediabetes and diabetes compared with normoglycaemic individuals.

Pericoronary adipose tissue: a novel therapeutic target in obesity-related coronary atherosclerosis.

Inflammation plays a crucial role in the development and destabilization of atherosclerotic plaques in coronary vessels. Adipose tissue is considered to act in paracrine manner, which modulates a number of physiological and pathophysiological processes. Perivascular adipose tissue has developed specific properties that distinguish it from the fat in other locations. Interestingly, its activity depends on several metabolic conditions associated with insulin resistance and weight gain. Particularly in obesity perivascular fat seems to change its character from a protective to a detrimental one. The present review analyzes literature in terms of the pathophysiology of atherosclerosis, with particular emphasis on inflammatory processes. Additionally, the authors summarize data about confirmed paracrine activity of visceral adipose tissue and especially about pericoronary fat influence on the vascular wall. The contribution of adiponectin, leptin and resistin is addressed. Experimental and clinical data supporting the thesis of outside-to-inside signaling in the pericoronary milieu are further outlined. Clinical implications of epicardial and pericoronary adipose tissue activity are also evaluated. The role of pericoronary adipose tissue in obesity-related atherosclerosis is highlighted. In conclusion, the authors discuss potential therapeutical implications of these novel phenomena, including adipokine imbalance in pericoronary adipose tissue in the setting of obesity, the influence of lifestyle and diet modification, pharmaceutical interventions and the growing role of microRNAs in adipogenesis, insulin resistance and obesity. Key teaching points: • adipose tissue as a source of inflammatory mediators • changes in the vascular wall as a result of outside-to-inside signaling • anatomy, physiology, and clinical implications of epicardial and pericoronary adipose tissue activity • adipokines and their role in obesity-related atherosclerosis • therapeutic perspectives and future directions.

Developing therapies for the metabolic syndrome: challenges, opportunities, and the unknown.

Metabolic syndrome refers to a clustering of established and emerging cardiovascular disease risk factors within a single individual. The established risk factors, such as obesity, diabetes, dyslipidaemia and hypertension, and other emerging risk factors are closely related to central obesity (especially intra-abdominal adiposity) and insulin resistance. However, debate continues about the very existence of the metabolic syndrome. Despite the controversies, many existing and new therapies are targeting the metabolic syndrome and component risk factors. To date, no therapies have been approved specifically for treating the metabolic syndrome. In this article some of the challenges and opportunities in developing therapies for the metabolic syndrome are discussed.