脂肪因子与代谢综合征

脂肪因子是一系列由脂肪组织分泌的生物活性物质,包括瘦素、抵抗素、脂联素、内肥素、肿瘤坏死因子、纤溶酶原激活物抑制因子和白介素-6等。脂肪因子的紊乱参与肥胖、糖尿病及动脉粥样硬化等多种代谢性疾病的发病过程。本文将着重讨论脂肪因子与代谢综合征的关联。     

Adipocyte-derived players in hematologic tumors: useful novel targets?

Introduction: Adipocytes and their products play essential roles in tumor establishment and progression. As the main cellular component of the bone marrow, adipocytes may contribute to the development of hematologic tumors.

Areas covered: This review summarizes experimental data on adipocytes and their interaction with various cancer cells. Special focus is set on the interactions of bone marrow adipocytes and normal and transformed cells of the hematopoietic system such as myeloma and leukemia cells. Current in vitro and in vivo data are summarized and the potential of novel therapeutic targets is critically discussed.

Expert opinion: Targeting lipid metabolism of cancer cells and adipocytes in combination with standard therapeutics might open novel therapeutic avenues in these cancer entities. Adipocyte-derived products such as free fatty acids and specific adipokines such as adiponectin may be vital anti-cancer targets in hematologic malignancies. However, available data on lipid metabolism is currently mostly referring to peripheral fat cell/cancer cell interactions and results need to be evaluated specifically for the bone marrow niche.     

Adipokine dysregulation and adipose tissue inflammation in human obesity

Obesity, a worldwide epidemic, confers increased risk for multiple serious conditions, including type 2 diabetes, cardiovascular diseases, nonalcoholic fatty liver disease and cancer. Adipose tissue is considered one of the largest endocrine organs in the body as well as an active tissue for cellular reactions and metabolic homeostasis rather than an inert tissue for energy storage. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a large number of hormones, cytokines, extracellular matrix proteins and growth and vasoactive factors, collectively termed adipokines that influence a variety of physiological and pathophysiological processes. In the obese state, excessive visceral fat accumulation causes adipose tissue dysfunctionality that strongly contributes to the onset of obesity‐related comorbidities. The mechanisms underlying adipose tissue dysfunction include adipocyte hypertrophy and hyperplasia, increased inflammation, impaired extracellular matrix remodelling and fibrosis together with an altered secretion of adipokines. This review describes how adipose tissue becomes inflamed in obesity and summarizes key players and molecular mechanisms involved in adipose inflammation.     

脂联素在骨代谢中的研究进展

上颌窦侧壁开窗提升是增加后牙骨量的有效治疗方式,其成功取决于新骨的形成和植体的长期存活率。影响上颌窦侧壁开窗提升后新骨形成及植体存活率的因素有很多,例如剩余牙槽骨高度、骨窗尺寸、骨窗覆盖方式、植骨方式等。有学者认为减小骨窗面积能保留更多骨壁,而覆盖生物屏障膜或游离骨块能防止软组织侵入,对于新骨生成和提高植体存活率有一定积极作用。有学者提出将具有分化潜能的成体干细胞、生长因子替代自体骨与其他骨替代材料混合应用以促进新骨形成。有学者提出同期种植时剩余牙槽骨高度的降低或不植骨的侧壁开窗提升方式不会影响新骨形成和植体存活率,从而扩大上颌窦侧壁开窗提升的手术适应证。本文就这几个因素展开讨论。     

Bacterial cell wall components regulate adipokine secretion from visceral adipocytes

Recent studies suggest a relationship between intestinal microbiota and metabolic syndromes; however, the underlying mechanism remains unclear. To clarify this issue, we assessed the effects of bacterial cell wall components on adiponectin, leptin and resistin secretion from rat visceral adipocytes in vitro. We also measured the relative population of Firmicutes and Bacteroidetes in fecal microbiota and the amount of fecal mucin as an intestinal barrier function, when mice were fed a high-fat diet. In the present study, we demonstrated that bacterial cell wall components affect the secretion of adipokines, depending on the presence of antigens from gram-positive or gram-negative bacteria. Lipopolysaccharide markedly inhibited adiponectin, leptin, and resistin secretion, whereas peptidoglycan increased adiponectin secretion and decreased resistin secretion in vitro. In vivo experiments showed that the high-fat diet increased the population of Firmicutes and decreased that of Bacteroidetes. In contrast, the high-fat diet downregulated the stool output and fecal mucin content. These results demonstrate that bacterial cell wall components affect the onset of metabolic syndromes by mediating the secretion of adipokines from visceral adipose tissue. Furthermore, we believe that metabolic endotoxemia is not due to the increasing dominance of gram-negative bacteria, Bacteroidetes, but due to the depression of intestinal barrier function.     

Asthma and obesity: a known association but unknown mechanism

The obese asthma phenotype is an increasingly common encounter in our clinical practice. Epidemiological data indicate that obesity increases the prevalence and incidence of asthma, and evidence that obesity precedes the development of asthma raises the possibility of a causal association. Obese patients with asthma experience more symptoms and increased morbidity compared with non-obese asthma patients. Despite more than a decade of research into this association, the exact mechanisms that underlie the interaction of obesity with asthma remain unclear. It is unlikely that the asthma-obesity association is simply due to comorbidities such as obstructive sleep apnoea or gastroesophageal reflux disease. Although inflammatory pathways are purported to play a role, there is scant direct evidence in humans that systemic inflammation modulates the behaviour of the asthmatic airway or the expression of symptoms in the obese. The role of non-eosinophilic airway inflammation also requires further study. Obesity results in important changes to the mechanical properties of the respiratory system, and these obesity-related factors appear to exert an additive effect to the asthma-related changes seen in the airways. An understanding of the various physiological perturbations that might be contributing to symptoms in obese patients with asthma will allow for a more targeted and rational treatment approach for these patients.     

The role of adipokines in periodontal infection and healing

Periodontitis is a chronic inflammatory disease of the periodontium, which is caused by pathogenic bacteria in combination with other risk factors. The bacteria induce an immunoinflammatory host response, which can lead to irreversible matrix degradation and bone resorption. Periodontitis can be successfully treated. To achieve regenerative periodontal healing, bioactive molecules, such as enamel matrix derivative (EMD), are applied during periodontal surgery. Recently, it has been shown that obesity is associated with periodontitis and compromised healing after periodontal therapy. The mechanisms underlying these associations are not well understood so far, but adipokines may be a pathomechanistic link. Adipokines are bioactive molecules that are secreted by the adipose tissue, and that regulate insulin sensitivity and energy expenditure, but also inflammatory and healing processes. It has also been demonstrated that visfatin and leptin increase the synthesis of proinflammatory and proteolytic molecules, whereas adiponectin downregulates the production of such mediators in periodontal cells. In addition, visfatin and leptin counteract the beneficial effects of EMD, whereas adiponectin enhances the actions of EMD on periodontal cells. Since visfatin and leptin levels are increased and adiponectin levels are reduced in obesity, these adipokines could be a pathomechanistic link whereby obesity and obesity‐related diseases enhance the risk for periodontitis and compromised periodontal healing. Recent studies have also revealed that adipokines, such as visfatin, leptin and adiponectin, are produced in periodontal cells and regulated by periodontopathogenic bacteria. Therefore, adipokines may also represent a mechanism whereby periodontal infections can impact on systemic diseases.     

Asthma and insulin resistance in children

Background and objective: Increased BMI is a risk factor for asthma in children and may be related to adipokines. Adipokines affect insulin‐stimulated glucose uptake in vitro but, to date there is little evidence for such a role in vivo. We explored relationships between obesity and allergic asthma in children. Methods: Twenty‐one allergic asthmatics (AA) and 10 non‐allergic healthy controls, aged 6–17.9 years were studied. AA group included children with a positive mannitol challenge test, >25 ppb of exhaled nitric oxide and a positive skin prick test. BMI z‐scores were calculated. Blood levels of insulin, glucose, leptin, resistin, tumour necrosis factor‐α, IL‐4, IL‐5 and IL‐6 were measured. Insulin resistance (IR) was estimated using the homeostasis model assessment (HOMA). Results: There was no significant difference in BMI z‐scores between AA and healthy controls (mean: 0.01 vs ?0.10). However, significant differences were found in the blood levels of IL‐6 (P = 0.05), IL‐4 (P = 0.04), IL‐5 (P = 0.01) and leptin (P = 0.02). IR was only found in the AA group (42.85%). Homeostasis model assessment insulin resistance (HOMA‐IR) was significantly related to IL‐6 (r = 0.44, P = 0.05) and tumour necrosis factor‐α (r = ?0.45, P = 0.05). Conclusions: IR was observed in AA. Our findings are suggestive of a complex interaction between the inflammatory state and adiposity, allergy and asthma.