中枢食欲调节研究进展

食欲调节网络的协调性摄食活动是维持人类生命的基本生理活动,食欲调节具有复杂而精细的调节机制,而下丘脑正是接受、整合与发放食欲调节信号、维持体重稳定的重要中枢.中枢神经系统或外周组织产生的具有促/抑食欲作用的神经内分泌因子在下丘脑形成复杂的食欲调节网络和相互投射的神经环路,对食欲进行精确的调控.不断完善下丘脑食欲调节区域,不断发现新的调控因子及其作用机制,对深入了解肥胖及糖尿病的病理生理机制及设计开发各种有效控制体重和血糖的药物有重大意义.     

The effects of weight loss strategies on gastric emptying and appetite control

The gastrointestinal tract plays an important role in the improved appetite control and weight loss in response to bariatric surgery. Other strategies which similarly alter gastrointestinal responses to food intake could contribute to successful weight management. The aim of this review is to discuss the effects of surgical, pharmacological and behavioural weight loss interventions on gastrointestinal targets of appetite control, including gastric emptying. Gastrointestinal peptides are also discussed because of their integrative relationship in appetite control. This review shows that different strategies exert diverse effects and there is no consensus on the optimal strategy for manipulating gastric emptying to improve appetite control. Emerging evidence from surgical procedures (e.g. sleeve gastrectomy and Roux‐en‐Y gastric bypass) suggests a faster emptying rate and earlier delivery of nutrients to the distal small intestine may improve appetite control. Energy restriction slows gastric emptying, while the effect of exercise‐induced weight loss on gastric emptying remains to be established. The limited evidence suggests that chronic exercise is associated with faster gastric emptying, which we hypothesize will impact on appetite control and energy balance. Understanding how behavioural weight loss interventions (e.g. diet and exercise) alter gastrointestinal targets of appetite control may be important to improve their success in weight management.     

下丘脑腺苷酸活化蛋白激酶与食欲和体重调节

腺苷酸活化蛋白激酶（AMPK）也称为真核细胞的“能量感受器”，下丘脑AMPK活性的下调能使摄食减少、体重降低，反之，摄食、体重增加。下丘脑AMPK能整合ghrelin等刺激食欲的信号和胰岛素、睫状神经营养因子等抑制食欲的信号，可能处于食欲、体重调节的中心环节，其机制可能在于改变了神经肽Y、刺鼠相关蛋白等的表达。对AMPK结构的阐明及对此信号通路的深入研究可能为肥胖的治疗提供新的靶点。     

Gut peptides and the regulation of appetite

There is a growing worldwide epidemic of obesity. Obese people have a higher incidence of type 2 diabetes and cardiovascular disease, and hence present increasing social, financial and health burdens. Weight loss is always difficult to achieve through lifestyle changes alone, and currently licensed anti-obesity drug treatments, such as orlistat and sibutramine, if tolerated, only achieve modest weight loss. Therefore, there is a need to identify more potent pharmacological targets. In the last 10 years, discoveries of new hormones such as leptin and ghrelin, together with greater understanding of previously described hormones such as cholecystokinin (CCK), pancreatic polypeptide (PP), peptide YY (PYY) and glucagon-like peptide 1 (GLP-1), have led to a rapid increase in our knowledge of the regulation of energy balance. Among the most important factors, controlling appetite and satiety are peptide hormones released from the gut. In this paper, we provide a full up-to-date overview of the current state of knowledge of this field, together with the potential of these peptides as drugs, or as other therapeutic targets, in the treatment of obesity. Finally, we propose an integrated model to describe the complex interplay of these hormones in the broader physiology of energy balance.     

胰高血糖素样肽-1与下丘脑食欲调节

下丘脑是神经内分泌中枢,也是食欲调节中枢.胰高血糖素样肽-1(GLP-1)是一种胃肠道激素,能够在下丘脑表达并对食欲中枢有调节作用.GLP-1作为一种厌食信号肽,通过促肾上腺皮质激素释放激素(CRH)通路、组胺神经元通路、神经肽和刺鼠相关蛋白(NPY/AgRP)以及前阿片黑皮质素原和可卡因-苯丙胺调节转录肽(POMC/CART)通路及AMP活化蛋白激酶(AMPK)介导的摄食负反馈信号通路参与调节摄食活动.针对GLP-1调节摄食作用机制的研究对肥胖、胰岛素抵抗和2型糖尿病的防治有重要的理论意义.     

Gastrointestinal targets of appetite regulation in humans

The aim of this paper is to describe and discuss relevant aspects of the assessment of physiological functions – and related biomarkers – implicated in the regulation of appetite in humans. A short introduction provides the background and the present state of biomarker research as related to satiety and appetite. The main focus of the paper is on the gastrointestinal tract and its functions and biomarkers related to appetite for which sufficient data are available in human studies. The first section describes how gastric emptying, stomach distension and gut motility influence appetite; the second part describes how selected gastrointestinal peptides are involved in the control of satiety and appetite (ghrelin, cholecystokinin, glucagon‐like peptide, peptide tyrosin‐tyrosin) and can be used as potential biomarkers. For both sections, methodological aspects (adequacy, accuracy and limitation of the methods) are described. The last section focuses on new developments in techniques and methods for the assessment of physiological targets involved in appetite regulation (including brain imaging, interesting new experimental approaches, targets and markers). The conclusion estimates the relevance of selected biomarkers as representative markers of appetite regulation, in view of the current state of the art.     

Cognitive training on eating behaviour and weight loss: A meta‐analysis and systematic review

Cognitive deficits play a role in the development and maintenance of overeating and obesity, and cognitive training in obesity refers to a family of interventions aimed at reducing overeating and obesity by improving these cognitive deficits. In this review, we synthesize the current literature on these issues by conducting a meta‐analysis of studies investigating the effects of cognitive trainings on eating behaviour and presenting a systematic review of studies investigating the effects of cognitive trainings on weight loss. We examined 66 independent experiments that examined the effects of cognitive training aimed at reducing cognitive bias or improving executive control on eating behaviour and weight loss. Overall, inhibition training, attention bias modification training, and episodic future thinking training significantly influenced eating behaviour; however, approach/avoidance training did not significantly influence eating behaviour. Moderator analyses indicated that the effect of inhibition training on eating behaviour was moderated by training task and food novelty, the effect of approach/avoidance training was moderated by food type, and the effect of episodic future thinking training was moderated by type of episodic future thinking. Literature reviewed on cognitive training and weight loss provided preliminary support for the effects of food‐specific inhibition training on weight loss from pre‐intervention to post intervention. However, because most of the included studies focused on short‐term outcomes in normal‐weight samples, longer duration studies in clinical populations (eg, individuals with obesity) are needed to examine the generalizability of these results.     

Eating behaviors in relation to gestational weight gain and postpartum weight retention: A systematic review

Preventing obesity is of utmost public health importance. This paper systematically reviews associations between eating behaviors and peripartum weight change. This knowledge is crucial in the development of interventions that reduce long‐term obesity, often triggered and boosted in the peripartum. Through MEDLINE, EMBASE, and Web of Science, we identified 20 studies that fulfilled inclusion criteria: studies on food cravings, disinhibition, restrained, external, emotional, uncontrolled, intuitive, or mindful eating in relation to gestational or postpartum weight among adult women. Higher gestational weight gain was associated with lower intuitive eating (in 3/3 studies) and higher restrained eating (in 4/11 studies), external eating (in 2/2 studies), emotional eating (in 3/4 studies), food cravings (in 3/3 studies), and disinhibition (in 1/3 studies). No association with uncontrolled eating was found (in one study). No studies on mindful eating and gestational weight were identified. Higher postpartum weight loss was associated with higher restrained (in 2/4 studies) and intuitive eating (in 1/1 study). No associations between postpartum weight and food cravings, disinhibition, and mindful eating were found. No studies on external, emotional and uncontrolled eating, and postpartum weight were identified. Concluding, certain eating behaviors might be related to peripartum weight change.     

A preliminary investigation of the role of melanin-concentrating hormone (MCH) and its receptors in appetite regulation of winter flounder (Pseudopleuronectes americanus)

In order to better understand the role of melanin-concentrating hormone (MCH) in the regulation of appetite in fish, the mRNAs of two forms of MCH, prepro-MCH and MCH2, and two forms of MCH receptors, MCH-R1 and MCH-R2, were isolated from winter flounder (Pseudopleuronectes americanus). In addition, the mRNA expressions of these peptides and their receptors were determined under fed and fasted conditions. Both MCHs are expressed in forebrain and midbrain, as well as peripheral tissues including gut and gonads. Both MCH-Rs are ubiquitously expressed in the brain and periphery. Fasting induced an increase in the expression levels of MCH and MCH-R1 mRNAs in optic tectum/thalamus and hypothalamus but had no effect on either MCH2 or MCH-R2 mRNA expressions. Our results suggest that MCH and MCH-R1, but not MCH2 and MCH-R2 might have a role in the regulation of appetite in flounder.     

Cocaine’s appetite for fat and the consequences on body weight

For many individuals in treatment for cocaine dependence, weight gain is a substantial problem during recovery. This weight gain causes significant distress and seems to increase the risk of relapse. The mechanisms underlying cocaine’s effects on weight remain elusive. It is widely assumed that this weight gain reflects a metabolic or behavioural compensatory response to the cessation of cocaine use. Here we challenge this assumption and outline potential mechanisms by which chronic cocaine use produces disturbances in the regulation of fat intake and storage, through its effects on the central and peripheral nervous systems, specifically the sympathetic nervous system. We hypothesize that the cocaine-induced alteration in fat regulation results in cocaine users developing a pronounced appetite for fatty food but keeps their fat mass low. This altered fat appetite subsequently leads to excessive weight gain when individuals enter treatment and stop using cocaine. Our aim is to shed light on the neurobiological mechanisms that may underlie the alterations in eating and fat regulation in cocaine-dependent individuals, to open up potential new avenues to support these individuals in recovery.     

Lifestyle factors and ghrelin: critical review and implications for weight loss maintenance

Ghrelin, the only known appetite‐stimulating hormone in humans, may be one factor involved in increased appetite, cravings and food intake following weight loss. Innovative strategies for suppressing ghrelin and decreasing appetite during weight loss maintenance are needed. Recent research has highlighted relationships between ghrelin, stress and lifestyle factors. The purposes of the current review are to (i) describe the current status of knowledge about ghrelin and lifestyle factors; (ii) critically examine research in this area, highlighting inconsistencies and methodological issues and (iii) discuss future directions and implications for obesity treatment. Based on Literature search using PsycINFO and Medline databases, we reviewed experimental studies on relationships between ghrelin, stress, exercise and sleep. Ghrelin levels are positively related to stress hormones, and stress management interventions including exercise and sleep may help to reduce acylated ghrelin and corresponding appetite. Behavioural interventions may offer a practical, cost‐effective alternative for reducing or stabilizing ghrelin levels after initial weight loss. Adding behavioural techniques designed to reduce ghrelin to traditional weight loss maintenance protocols may help individuals to maintain weight loss. Future directions for investigating relationships between ghrelin and behavioural factors, examining the efficacy of behavioural programmes in reducing ghrelin and improving weight loss maintenance are discussed.     

Relationship of glucose regulation to changes in weight: a systematic review and guide to future research

Although weight gain and obesity are risk factors for poor glucose regulation, the relationship, if any, of glucose regulation to changes in weight is not well understood. The purpose of this study was to conduct a systematic review of research examining the relationship of glucose regulation to changes in weight in human‐based studies and to provide guidelines for future research in this area. We searched electronic databases and reference sections of relevant articles, including both diabetic and non‐diabetic populations, to locate all the literature published before February 2010, and then conducted a systematic review across studies to compare the research designs and findings. The 22 studies meeting our criteria for review generally supported the relationship of glucose regulation to changes in weight. Three studies reported that poor glucose regulation is associated with weight gain; 12 studies concluded that poor glucose regulation is associated with weight loss; 5 showed complex relationships depending on age, sex, or race/ethnicity; and 2 suggested no relationship. The diverse findings may imply that the direction (negative or positive) of the relationship may depend on specific conditions. More research focused on different subpopulations may provide more definitive information supplemental to the current preliminary findings. Recommendations regarding future research in this particular area are provided in the discussion. Copyright © 2010 John Wiley & Sons, Ltd.     

Mindful eating and common diet programs lower body weight similarly: Systematic review and meta‐analysis

Common strategies for reducing body weight rely on limiting energy intake and restricting food choices. However, these strategies have often been proven ineffective in achieving long‐term and sustainable weight reduction. More recently, mindful eating as an alternative weight management strategy has gained increasing attention, yet systematic reviews on intuitive or mindful eating published so far present contradictory results. We performed a systematic review and meta‐analysis on randomized controlled trials on weight loss programs based on mindful or intuitive eating. We analyzed results using meta‐regressions. We included a total of 10 studies and found a significant weight loss effect of mindful/intuitive eating strategies compared with nonintervention controls (?0.348 kg, 95% CI: ?0.591 to ?0.105, P = 0.005). However, there was no difference compared with conventional diet programs (P = 0.99). Reduction of BMI (?0.137 kg/m², 95% CI: ?0.365 to 0.091, P = 0.240) or waist circumference (?0.358 cm, 95% CI: ?0.916 to 0.200, P = 0.209) were not statistically significant. Mindful/intuitive eating could be a practical approach to weight control. Limitations of this study include the unbalanced sex, origin, place of residence of the participants, and the short duration of interventions. Future research should aim at investigating long‐term effects and include a more heterogeneous study population.     

Modern sedentary activities promote overconsumption of food in our current obesogenic environment

Achieving body‐weight stability is certainly challenging in today's obesogenic environment. Every day we are surrounded and affected by stimuli that act on our behaviour. A common feature of these stimuli is that they increase our comfort and well‐being, but unfortunately they promote a positive caloric balance. Intriguingly, the preponderance of sedentary lifestyles is not only a matter of the amount of calories expended. A careful examination of modern sedentary activities reveals that they also promote overconsumption of food. This is particularly the case with television viewing, video game playing, cognitive working, music listening and short sleeping. Moreover, the increased food intake in the absence of hunger observed with the practice of these modern‐life activities emphasizes that the hedonic value of food intake plays an important role. These observations suggest that our quest for reward and pleasure is not fine tuned to our biology, and the development of coping strategies is needed.