Organ-specific alterations in circadian genes by vertical sleeve gastrectomy in an obese diabetic mouse model

Current therapies for obesity and related complications have been shown to have limited benefits,including unsatisfactory weight loss and poor metabolic improvement.With recent developments in bariatric surgery,promising advancements have been made in clinical and scientific research,particularly in the management of obesity and diabetes.Vertical sleeve gastrectomy(VSG)has become increasingly popular due to its safety,simplicity,

Increased BMR in Overweight and Obese Patients with Type 2 Diabetes may Result from an Increased Fat-free Mass

The study aimed to determine the relationships between the basal metabolic rate（BMR） and body composition of overweight and obese Chinese adults with type 2 diabetes mellitus（DM）. This cross-sectional clinical study enrolled 193 Chinese adults with type 2 DM who were overweight（24 kg/m2≤BMI〈28 kg/m2, n=99）, or obese（BMI ≥28 kg/m2, n=94）. Ninety-seven adults with normal BMIs, including 50 DM patients and 47 healthy adults, were recruited as a control group. BMR was measured by indirect calorimetry; predicted BMR was calculated according to the Schofield equation; and the relationships between BMR, body composition, and biochemical results were determined by the Pearson correlation. The results showed that obese DM patients had significantly higher BMRs than both overweight patients（P〈0.05） and patients with normal BMI did（P〈0.05）. The measured BMR was significantly lower than the predicted BMR（P〈0.05） in all groups. Obese and overweight DM patients had significantly greater weight, waist circumference, hip circumference, BMI, body surface area, body fat percentage, fat mass, and fat-free mass than patients with normal BMI. Except for waist circumference, these body composition measurements were significantly increased in obese DM patients when compared with those in overweight DM patients（P〈0.05）. Fat-free mass was closely correlated with BMR in both DM patients（r=0.874, P〈0.01） and in healthy controls（r=0.902, P〈0.01）. It was concluded that overweight and obese Chinese adults with type 2 DM had increased BMRs compared with normal-weight controls, which may result from the difference in fat-free mass.

Waist Circumference-dependent Peripheral Monocytes Change after Gliclazide Treatment for Chinese Type 2 Diabetic Patients

Gliclazide used for the treatment of type 2 diabetes mellitus（T2DM） stimulates insulin secretion and influences peripheral blood monocytes.The roles of gliclazide in peripheral monocytes of newly diagnosed T2 DM patients were investigated in this study.A total of 105 newly diagnosed T2 DM patients with no history of antihyperglycemic medication were treated with gliclazide-modified release for 16 weeks.The total and differential leukocyte profiles of peripheral blood were measured at baseline and week 16.The peripheral blood monocyte count at week 16 was significantly lower than that at baseline（P=0.019）.Peripheral monocytes level at baseline was positively correlated with waist circumference.After gliclazide treatment,the peripheral monocytes were decreased [（320.09±15.13）×10~6/L vs.（294.19±14.22）×10~6/L] in non-abdominal obesity group,but increased in abdominal obesity group [（344.36±17.24）×10~6/L vs.（351.87±16.93）×10~6/L].Compared with non-abdominal obese patients,abdominal obese patients showed higher Δmonocytes（P=0.046） and Δacute insulin secretion（P=0.049）,but lower ΔHb A1c（P=0.047）.There was significantly positive correlation between Δmonocytes and Δacute insulin secretion（P=0.015）,which disappeared after adjusting for age,waist circumference and dosage at baseline.In conclusion,waist circumference is correlated with peripheral monocyte change after gliclazide treatment in Chinese newly diagnosed T2 DM patients.Peripheral monocytes are decreased in non-abdominal obesity group and increased in abdominal obesity group after gliclazide treatment.

Leptin: a multifunctional hormone

Leptin is the protein product encoded by the obese (ob)gene. It is a circulating hormone produced primarily by the adipose tissue. ob/ob mice with mutations of the gene encoding leptin become morbidly obese, infertile, hyperphagic, hypothermic,and diabetic. Since the cloning of leptin in 1994, our knowledge in body weight regulation and the role played by leptin has increased substantially. We now know that leptin signals through its receptor, OB-R, which is a member of the cytokine receptor superfamily. Leptin serves as an adiposity signal to inform the brain the adipose tissue mass in a negative feedback loop regulating food intake and energy expenditure. Leptin also plays important roles in angiogenesis, immune function, fertility and bone formation. Humans with mutations in the gene encoding leptin are also morbidly obese and respond to leptin treatment,demonstrating that enhancing or inhibiting leptin’s activities in vivo may have potential therapeutic benefits.

Emerging roles of cardiolipin remodeling in mitochondrial dysfunction associated with diabetes,obesity,and cardiovascular diseases

Cardiolipin （CL） is a phospholipid exclusively localized in inner mitochondrial membrane where it is required for oxidative phosphorylation, ATP synthesis, and mitochondrial bioenergetics. The biological functions of CL are thought to depend on its acyl chain composition which is dominated by linoleic acids in metabolically active tissues. This unique feature is not derived from the de novo biosynthesis of CL, rather from a remodeling process that involves in phospholipases and transacylase/acyltransferase. The remodeling process is also believed to be responsible for generation of CL species that causes oxidative stress and mitochondrial dysfunction. CL is highly sensitive to oxidative damages by reactive oxygen species （ROS） due to its high content in polyunsaturated fatty acids and location near the site of ROS production. Consequently, pathological remodeling of CL has been implicated in the etiology of mitochondrial dysfunction commonly associated with diabetes, obesity, heart failure, neurodegeneration, and aging that are characterized by oxidative stress, CL deficiency, and abnormal CL species. This review summarizes recent progresses in molecular, enzymatic, lipidomic, and metabolic studies that support a critical regulatory role of pathological CL remodeling as a missing link between oxidative stress and mitochondrial dysfunction in metabolic diseases and aging.

Association of TCF7L2 and GCG Gene Variants with Insulin Secretion,Insulin Resistance,and Obesity in New-onset Diabetes

This cohort study was designed to evaluate the association of transcription factor 7-like 2 （TCF7L2） and proglucagon gene （GCG） variants with disordered glucose metabolism and the incidence of type 2 diabetes mellitus （T2DM） in a rural adult Chinese population. A total of 7,751 non-T2DM participants 〉18 years old genotyped at baseline were recruited. The same questionnaire interview and physical and blood biochemical examinations were performed at both baseline and follow-up. During a median 6 years of follow-up, T2DM developed in 227 participants. After adjustment for potential contributory factors, nominally significant associations were seen between 3T genotype and the recessive model of TCFTI.2 rs7903146 and increased risk of T2DM [hazard ratio （HR）=4.068, 95% confidence interval （CI）： 1.270-13.026; HR=4.051, 95% CI： 1.268-12.946, respectively]. The TT genotype of rs7903146 was also significantly associated with higher fasting plasma insulin level and the homeostasis model assessment of insulin resistance in case of new-onset diabetes. In addition, the TCF7L2 rs290487 TT genotype was associated with abdominal obesity and the GCG rs12104705 CC genotype was associated with both general obesity and abdominal obesity in case of new-onset diabetes.

Advances in Acupuncture and its Associated Therapies for the Prevention and Treatment of Obesity Type 2 Diabetes Mellitus

Obesity type 2 diabetes mellitus is a common metabolic disease in clinical practice,and its prevalence is increasing rapidly with the aging of the population and changes in lifestyle.Acupuncture,as a distinctive therapy,has its unique advantages in the treatment of obesity type 2 diabetes and has an irreplaceable role in a variety of treatment methods.The author organized the literature on acupuncture and its related therapies to prevent and treat obesity type 2 diabetes in recent years and found that acupuncture and its associated therapies to prevent and treat obesity type 2 diabetes mainly include:simple acupuncture,electroacupuncture,acupoint catgut embedding therapy,auricular-plaster therapy and other treatments,all of which can safely and effectively improve clinical symptoms,acupuncture and its related therapies to treat obesity type 2 diabetes has a broad prospect,worthy of further clinical promotion.

Obesity and the risk of cardiovascular disease and diabetes mellitus

The increasing prevalence of obesity worldwide has many experts concerned about the worsening health of a large proportion of the population. It is well recognized that obesity is associated with a higher mortality, an increased risk of hypertension and hyperlipidemia, cardiovascular disease, diabetes mellitus, osteoarthritis, gall bladder disease and possibly some cancers. Currently it is estimated that over two thirds of adults in the United States are overweight and nearly one third are clinically obese.1 Of special concern is the rapid increase in obesity among children. Other countries both developed and developing are experiencing similar trends.……

Morbid Obesity in Diabetes Mellitus Type 2 and Exenatide

Worldwide, the prevalence of diabetes and obesity is increasing in recent years in developed countries. The first step of treatment is changes in lifestyle and in case of failure to initiate drug treatment. In our case, the patient with morbid obesity and glucose intolerance to metformin therapy was initiated without achieving weight loss and loss of glycemic control after 6 months of treatment. It was decided to add exenatide as an alternative to bariatric surgery. At the end of the study (12 months), it showed a weight reduction of 20.8% (Table 1), 20.83% BMI, glycosylated hemoglobin decrease of 2 points, and improved the lipid profile. So exenatide may be an acceptable option in the use of patient profile. It would be necessary to seek a new alternative treatment with minimal side effects and less healthcare costs.

Therapy to Obese Type 2 Diabetes Mellitus:How Far Will We Go Down the Wrong Road?

Traditional glucose-lowering chemical agents, including various types of insulin and insulin secretagogues, insulin sensitizers, gliptins, etc., are based on diabetic pathogenesis of insulin resistance(IR) and islet insufficiency. Numerous evidence-based medical studies have shown that these traditional hypoglycemic chemical agents do not provide cardiovascular benefit to patients with type 2 diabetes mellitus(T2 DM) and may even increase the risk of all-cause mortality. Based on research evidence published to date, these studies show that overload of energy could increase the incidence and prevalence of T2 DM, and reduction in the heat load can significantly reduce the incidence of T2 DM. Therefore, the essence of T2 DM is heat overload, meaning heat overload is the etiology of obese T2 DM. At the same time, results of numerous studies show that heat overloading is the cause of IR. IR and islet dysfunction are protective factors in intervening with heat overload.These drugs, which are based on the mechanisms of IR and islet insufficiency, increase caloric reserve and cause or worsen obesity, which is equivalent to exacerbating the basic etiology and the cardiovascular risk factor of T2 DM. Thus, a reasonable strategy for prevention and treatment of obese T2 DM appears to promote the negative balance of calories and the elimination of caloric reserves. Chinese herbal medicines can promote negative balance of heat in many aspects, which can bring new hope for prevention and treatment of T2 DM.

Targeting mitochondrial biogenesis for preventing and treating insulin resistance in diabetes and obesity:Hope from natural mitochondrial nutrients

Insulin resistance is an important feature of type 2 diabetes and obesity. The underlying mechanisms of insulin resistance are still unclear. Mitochondrial dysfunction,

Eating Breakfast May Stave Off Obesity,Diabetes

选注者言:在过去的8年中,Pereira博士对近3000名年龄在25至37岁之间的成年人的饮食习惯及健康状况进行了跟踪调查。结果发现,与那些偶尔吃早餐或根本不吃早餐的人相比,每天坚持吃早餐的人患肥胖症和糖尿病的几率降低了35％至50％。研究人员说,不吃早餐容易导致人体内胰岛素的缺失。而它的缺失往往是糖尿病的先兆。另一方面,吃早餐有助于控制饮食,避免人在一天中的其余时间因为吃地过多而逐渐变得肥胖。

Autophagic Clearance of Lipid Droplets Alters Metabolic Phenotypes in a Genetic Obesity–Diabetes Mouse Model

Lipid droplets(LDs)are intracellular organelles that store neutral lipids,and their aberrant accumulation is associated with many diseases including metabolic disorders such as obesity and diabetes.Meanwhile,the potential pathological contribu-tions of LDs in these diseases are unclear,likely due to a lack of chemical biology tools to clear LDs.We recently developed LD-clearance small molecule compounds,Lipid Droplets·AuTophagy TEthering Compounds(LD·ATTECs),that are able to induce autophagic clearance of LDs in cells and in the liver of db/db(C57BL/6J Leprdb/Leprdb)mouse model,which is a widely used genetic model for obesity–diabetes.Meanwhile,the potential effects on the metabolic phenotype remain to be elucidated.Here,using the metabolic cage assay and the blood glucose assay,we performed phenotypic characteriza-tion of the effects of the autophagic degradation of LDs by LD·ATTECs in the db/db mouse model.The study reveals that LD·ATTECs increased the oxygen uptake of mice and the release of carbon dioxide,enhanced the heat production of animals,partially enhanced the exercise during the dark phase,decreased the blood glucose level and improved insulin sensitivity.Collectively,the study characterized the metabolic phenotypes induced by LD·ATTECs in an obesity–diabetes mouse model,revealing novel functional impacts of autophagic clearance of LDs and providing insights into LD biology and obesity–dia-betes pathogenesis from the phenotypic perspective.