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New practice in semaglutide on type-2 diabetes and obesity: clinical evidence and expectation

《医学前沿（英文）》 2022年第16卷第1期页码 17-24 doi: 10.1007/s11684-021-0873-2

摘要： Obesity is an important risk factor of type 2 diabetes (T2D), which has become an important factor threatening human health. However, no perfect drug choice for obesity exists. Semaglutide is a kind of human glucagon-like peptide-1 (GLP-1) analog that promotes insulin secretion while inhibiting glucagon secretion through a glucose concentration-dependent mechanism. GLP-1 can also delay stomach emptying and suppress appetite to help lose weight. This review summarizes clinical evidence of the semaglutide effect on T2D and obesity and establishes expectations on future clinical trials for obesity treatment.

关键词： semaglutide type 2 diabetes obesity

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Beneficial metabolic activities of inflammatory cytokine interleukin 15 in obesity and type 2 diabetes

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《医学前沿（英文）》 2015年第9卷第2期页码 139-145 doi: 10.1007/s11684-015-0377-z

摘要：

In obesity, chronic inflammation is believed to induce insulin resistance and impairs adipose tissue function. Although this view is supported by a large body of literature, it has been challenged by growing evidence that pro-inflammatory cytokines may favor insulin sensitivity through induction of energy expenditure. In this review article, interleukin 15 (IL-15) is used as a new example to explain the beneficial effects of the pro-inflammatory cytokines. IL-15 is secreted by multiple types of cells including macrophages, neutrophils and skeletal muscle cells. IL-15 expression is induced in immune cells by endotoxin and in muscle cells by physical exercise. Its transcription is induced by transcription factor NF-κB. IL-15 binds to its receptor that contains three different subunits (α, β and γ) to activate JAK/STAT, PI3K/Akt, IKK/NF-κB and JNK/AP1 pathways in cells. In the regulation of metabolism, IL-15 reduces weight gain without inhibiting food intake in rodents. IL-15 suppresses lipogenesis, stimulates brown fat function, improves insulin sensitivity through weight loss and energy expenditure. In human, circulating IL-15 is negatively associated with body weight. In the immune system, IL-15 stimulates proliferation and differentiation of T cells, NK cells, monocytes and neutrophils. In the anti-obesity effects of IL-15, T cells and NK cells are not required, but leptin receptor is required. In summary, evidence from human and rodents supports that the pro-inflammatory cytokine IL-15 may enhance energy expenditure to protect the body from obesity and type 2 diabetes. The mechanism of IL-15 action remains to be fully uncovered in the regulation of energy expenditure.

关键词： inflammation obesity cytokine energy expenditure insulin resistance

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Obesity in China: its characteristics, diagnostic criteria, and implications

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《医学前沿（英文）》 2015年第9卷第2期页码 129-133 doi: 10.1007/s11684-015-0387-x

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Interplay between diet and genetic susceptibility in obesity and related traits

Tiange Wang, Min Xu, Yufang Bi, Guang Ning

《医学前沿（英文）》 2018年第12卷第6期页码 601-607 doi: 10.1007/s11684-018-0648-6

摘要：

The incidence of obesity has been rapidly increasing, and this condition has become a major public health threat. A substantial shift in environmental factors and lifestyle, such as unhealthy diet, is among the major driving forces of the global obesity pandemic. Longitudinal studies and randomized intervention trials have shown that genetic susceptibility to obesity may interact with dietary factors in relation to the body mass index and risk of obesity. This review summarized data from recent longitudinal studies and intervention studies on variations and diets and discussed the challenges and future prospects related to this area and public health implications.

关键词： diet genetic susceptibility obesity interaction

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Advancement in genetic variants conferring obesity susceptibility from genome-wide association studies

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《医学前沿（英文）》 2015年第9卷第2期页码 146-161 doi: 10.1007/s11684-014-0373-8

摘要：

Obesity prevalence has increased in recent years. Lifestyle change fuels obesity, but genetic factors cause more than 50% of average variations in obesity. The advent of genome-wide association studies (GWAS) has hastened the progress of polygenic obesity research. As of this writing, more than 73 obesity susceptibility loci have been identified in ethnic groups through GWAS. The identified loci explain only 2% to 4% of obesity heritability, thereby indicating that a large proportion of loci remain undiscovered. Thus, the next step is to identify and confirm novel loci, which may exhibit smaller effects and lower allele frequencies than established loci. However, achieving these tasks has been difficult for researchers. GWAS help researchers discover the causal loci. Moreover, numerous biological studies have been performed on the polygenic effects on obesity, such as studies on fat mass- and obesity-associated gene (FTO), but the role of these polygenic effects in the mechanism of obesity remains unclear. Thus, obesity-causing variations should be identified, and insights into the biology of polygenic effects on obesity are needed.

关键词： obesity genetics genome-wide association studies body mass index fat mass- and obesity-associated gene

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Mechanism of insulin resistance in obesity: a role of ATP

《医学前沿（英文）》 2021年第15卷第3期页码 372-382 doi: 10.1007/s11684-021-0862-5

摘要： Obesity increases the risk of type 2 diabetes through the induction of insulin resistance. The mechanism of insulin resistance has been extensively investigated for more than 60 years, but the essential pathogenic signal remains missing. Existing hypotheses include inflammation, mitochondrial dysfunction, hyperinsulinemia, hyperglucagonemia, glucotoxicity, and lipotoxicity. Drug discoveries based on these hypotheses are unsuccessful in the development of new medicines. In this review, multidisciplinary literature is integrated to evaluate ATP as a primary signal for insulin resistance. The ATP production is elevated in insulin-sensitive cells under obese conditions independent of energy demand, which we have named “mitochondrial overheating.” Overheating occurs because of substrate oversupply to mitochondria, leading to extra ATP production. The ATP overproduction contributes to the systemic insulin resistance through several mechanisms, such as inhibition of AMPK, induction of mTOR, hyperinsulinemia, hyperglucagonemia, and mitochondrial dysfunction. Insulin resistance represents a feedback regulation of energy oversupply in cells to control mitochondrial overloading by substrates. Insulin resistance cuts down the substrate uptake to attenuate mitochondrial overloading. The downregulation of the mitochondrial overloading by medicines, bypass surgeries, calorie restriction, and physical exercise leads to insulin sensitization in patients. Therefore, ATP may represent the primary signal of insulin resistance in the cellular protective response to the substrate oversupply. The prevention of ATP overproduction represents a key strategy for insulin sensitization.

关键词： type 2 diabetes energy expenditure mitochondria hyperinsulinemia hyperglucagonemia AMPK

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《医学前沿（英文）》 2017年第11卷第3期页码 340-348 doi: 10.1007/s11684-017-0570-3

摘要：

In light of the rapid increase in the number of obesity incidences worldwide, obesity has become an independent risk factor for chronic kidney disease. Obesity-related glomerulopathy (ORG) is characterized by glomerulomegaly in the presence or absence of focal and segmental glomerulosclerosis lesions. IgM and complement 3 (C3) nonspecifically deposit in lesions without immune-complex-type deposits during ORG immunofluorescence. ORG-associated glomerulomegaly and focal and segmental glomerulosclerosis can superimpose on other renal pathologies. The mechanisms under ORG are complex, especially hemodynamic changes, inflammation, oxidative stress, apoptosis, and reduced functioning nephrons. These mechanisms synergize with obesity to induce end-stage renal disease. A slow increase of subnephrotic proteinuria (<3.5 g/d) is the most common clinical manifestation of ORG. Several treatment methods for ORG have been developed. Of these methods, renin–angiotensin–aldosterone system blockade and weight loss are proven effective. Targeting mitochondria may offer a novel strategy for ORG therapy. Nevertheless, more research is needed to further understand ORG.

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Epidemic obesity in children and adolescents: risk factors and prevention

Eun Young Lee, Kun-Ho Yoon

《医学前沿（英文）》 2018年第12卷第6期页码 658-666 doi: 10.1007/s11684-018-0640-1

摘要： The prevalence of obesity among children and adolescents (aged 2–18 years) has increased rapidly, with more than 100 million affected in 2015. Moreover, the epidemic of obesity in this population has been an important public health problem in developed and developing countries for the following reasons. Childhood and adolescent obesity tracks adulthood obesity and has been implicated in many chronic diseases, including type 2 diabetes, hypertension, and cardiovascular disease. Furthermore, childhood and adolescent obesity is linked to adulthood mortality and premature death. Although an imbalance between caloric intake and physical activity is a principal cause of childhood and adolescent obesity, environmental factors are exclusively important for development of obesity among children and adolescents. In addition to genetic and biological factors, socioenvironmental factors, including family, school, community, and national policies, can play a crucial role. The complexity of risk factors for developing obesity among children and adolescents leads to difficulty in treatment for this population. Many interventional trials for childhood and adolescent obesity have been proven ineffective. Therefore, early identification and prevention is the key to control the global epidemic of obesity. Given that the proportion of overweight children and adolescents is far greater than that of obesity, an effective prevention strategy is to focus on overweight youth, who are at high risk for developing obesity. Multifaceted, comprehensive strategies involving behavioral, psychological, and environmental risk factors must also be developed to prevent obesity among children and adolescents.

关键词： obesity children adolescents epidemiology risk factor prevention

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Postnatal feeding with high-fat diet induces obesity and precocious puberty in C57BL/6J mouse pups: anovel model of obesity and puberty

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《医学前沿（英文）》 2017年第11卷第2期页码 266-276 doi: 10.1007/s11684-017-0530-y

摘要：

Childhood obesity and obesity-related metabolic complications are induced by a high-fat postnatal diet. The lack of a suitable animal model, however, remains a considerable challenge in obesity studies. In the current study, we provided high-fat diet (HFD) to dams during lactation and to pups after weaning. We also developed a novel model of C57BL/6J mouse pups with HFD-induced postnatal obesity. Results showed that feeding with HFD induces fat deposition and obesity in pups. Furthermore, HFD more potently increased the body weight (BW) of male than female pups. HFD-fed female pups were obese, underwent precocious puberty, and showed increased kisspeptin expression in the hypothalamus. However, parental obesity and precocious puberty exerted no synergistic effects on the HFD-induced postnatal weight gain and puberty onset of the pups. Interestingly, some HFD-fed litters with normal BW also exhibited precocious puberty. This finding suggested that diet composition but not BW triggers puberty onset. Our model suggests good construction validity of obesity and precocious puberty. Furthermore, our model can also be used to explore the mutual interactions between diet–induced postnatal childhood obesity and puberty.

关键词： postnatal HFD feeding obesity kisspeptin HPG axis precocious puberty

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Analyzing the distinguishing factors that affect childhood obesity in South Korea

So Jung Yang, Hun-Sung Kim, Kun-Ho Yoon

《医学前沿（英文）》 2018年第12卷第6期页码 707-716 doi: 10.1007/s11684-018-0660-x

摘要：

Understanding obesity in children is crucial because it can lead to adulthood obesity and result in fatal chronic diseases. Distinctive factors associated with obesity in adults have been described, but distinctive factors related to children remain unclear. We analyzed the correlation between the percentage of body mass index and lifestyle habits by conducting surveys on physical, nutritional, and psychological factors, and we used annual physical examination data to compare different traits among elementary school students (n = 197) and middle school students (n = 461). Our study revealed that the computing hours in elementary school students with overweight and obesity were significantly correlated with the percentage of body mass index (r = 0.29 on school days and r = 0.35 on days off, all P<0.05). No statistically significant difference was found (all P>0.05) in the computing hours of middle school students with overweight and obesity. Childhood obesity can cause depression and reduce children’s quality of life because of their distorted body perception. In conclusion, physical factors directly affecting childhood obesity and psychological and environmental factors surrounding a child should be considered.

关键词： screen time quality of life eating habits childhood obesity percentage of body mass index

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Obesity and overweight prevalence and its association with undiagnosed hypertension in Shanghai population

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《医学前沿（英文）》 2012年第6卷第3期页码 322-328 doi: 10.1007/s11684-012-0204-8

摘要：

The aim of this study was to determine the prevalence of overweight and obese subjects in the Shanghai population of China and its association with undiagnosed hypertension, by taking age, gender and place of residence (urban or suburban) into account. A cross-sectional population-based survey was conducted in 2007. The sample included 13 359 participants aged 15–69 years. Weight, height, and blood pressure were recorded, and information about gender, age and place of residence was obtained. Overweight and obesity prevalence were calculated by the body mass index (BMI) definition recommended by Working Group on Obesity in China (normal weight, 18.5–23.9 kg/m²; overweight, 24–27.9 kg/m²; obesity,≥28 kg/m²). Undiagnosed hypertension was defined by China criteria in accord with that of WHO-ISH (subjects with systolic pressure≥140 mmHg, and/or diastolic pressure≥90 mmHg). Multiple logistic regression analyses were used to assess the association of overweight or obesity with undiagnosed hypertension by adjusting for age, gender and place of residence. The overall overweight, obesity, and undiagnosed hypertension prevalence were 27.6% (95% CI: 26.8–28.4), 6.6% (95% CI: 6.2–7.0), and 15.5% (95% CI: 14.9–16.1), respectively. Compared to normal weight subjects, the odds ratios (OR) for subjects who were overweight and had hypertension was 2.33 (95% CI: 2.10–2.59); that for obesity and hypertension was 4.27 (95% CI: 3.66–4.99). These data suggest that overweight and obesity prevalence and their association with undiagnosed hypertension are high in our study population.

关键词： overweight obesity undiagnosed hypertension prevalence association

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The mechanisms linking adiposopathy to type 2 diabetes

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《医学前沿（英文）》 2013年第7卷第4期页码 433-444 doi: 10.1007/s11684-013-0288-9

摘要：

Obesity is defined as excessive accumulation of body fat in proportion to body size. When obesity occurs, the functions of adipose tissue may be deregulated, which is termed as adiposopathy. Adiposopathy is an independent risk factor for many diseases, including diabetes and cardiovascular diseases. In overweight or obese subjects with adiposopathy, hyperlipidemia exerts lipotoxicity in pancreatic islet and liver and induces pancreatic β cell dysfunction and liver insulin resistance, which are the decisive factors causing type 2 diabetes. Moreover, adipokines have been shown to play important roles in the regulation of glucose homeostasis. When adiposopathy occurs, abnormal changes in the serum adipokine profile correlate with the development and progression of pancreatic β cell dysfunction and insulin resistance in peripheral tissue. The current paper briefly discusses the latest findings regarding the effects of adiposopathy-related lipotoxicity and cytokine toxicity on the development of type 2 diabetes.

关键词： obesity adiposopathy lipotoxicity adipokines diabetes

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Molecular mechanisms of fatty liver in obesity

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《医学前沿（英文）》 2015年第9卷第3期页码 275-287 doi: 10.1007/s11684-015-0410-2

摘要：

Nonalcoholic fatty liver disease (NAFLD) covers a spectrum of liver disorders ranging from simple steatosis to advanced pathologies, including nonalcoholic steatohepatitis and cirrhosis. NAFLD significantly contributes to morbidity and mortality in developed societies. Insulin resistance associated with central obesity is the major cause of hepatic steatosis, which is characterized by excessive accumulation of triglyceride-rich lipid droplets in the liver. Accumulating evidence supports that dysregulation of adipose lipolysis and liver de novo lipogenesis (DNL) plays a key role in driving hepatic steatosis. In this work, we reviewed the molecular mechanisms responsible for enhanced adipose lipolysis and increased hepatic DNL that lead to hepatic lipid accumulation in the context of obesity. Delineation of these mechanisms holds promise for developing novel avenues against NAFLD.

关键词： nonalcoholic fatty liver disease insulin resistance obesity

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Leptin signaling and leptin resistance

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《医学前沿（英文）》 2013年第7卷第2期页码 207-222 doi: 10.1007/s11684-013-0263-5

摘要：

Leptin is secreted into the bloodstream by adipocytes and is required for the maintenance of energy homeostasis and body weight. Leptin deficiency or genetic defects in the components of the leptin signaling pathways cause obesity. Leptin controls energy balance and body weight mainly through leptin receptor b (LEPRb)-expressing neurons in the brain, particularly in the hypothalamus. These LEPRb-expressing neurons function as the first-order neurons that project to the second-order neurons located within and outside the hypothalamus, forming a neural network that controls the energy homeostasis and body weight. Multiple factors, including inflammation and endoplasmic reticulum (ER) stress, contribute to leptin resistance. Leptin resistance is the key risk factor for obesity. This review is focused on recent advance about leptin action, leptin signaling, and leptin resistance.

关键词： leptin signaling leptin receptor energy balance leptin resistance obesity

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Brown and beige fat: the metabolic function, induction, and therapeutic potential

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《医学前沿（英文）》 2015年第9卷第2期页码 162-172 doi: 10.1007/s11684-015-0382-2

摘要：

Adipose tissue is an important organ for energy homeostasis. White adipose tissue stores energy in the form of triglycerides, whereas brown adipocytes and recently identified beige adipocytes are specialized in dissipating energy by thermogenesis or contribution to dispose glucose and clear triglycerides in blood. The inverse correlation between the brown adipose tissue activity and body mass suggests its protective role against body fat accumulation. Thus, recruitment and activation of brown or beige adipose tissue become particularly appealing targets for increasing energy expenditure. Angiogenesis and sympathetic nerve signals are the fundamental determinants for brown and beige adipose tissue development, as well as for their metabolic functions. Secretary factors including BMPs can induce the development, the activation of brown or beige adipose tissue, which seem to be promising for therapeutic development.

关键词： brown adipocyte beige adipocyte metabolism obesity