Saira Hameed

Gut hormones and appetite control

The gastrointestinal tract is the largest endocrine organ in the body. It secretes more than 20 different peptide hormones, which serve both a local regulatory function and provide a means by which the gut can regulate appetite and satiety. As the worldwide prevalence of obesity reaches epidemic proportions, the importance of delineating the mechanisms which regulate food intake becomes even more urgent. There is now a substantial body of work in both rodent and human models demonstrating the effects of these peptides on appetite and work is underway to therapeutically manipulate the gut-brain axis for the treatment of obesity. In addition, it may also be possible to use our understanding of the entero-endocrine system to treat calorie-deficient states.

Kisspeptin and fertility

The kisspeptins are a family of peptide hormones, which in recent years have been shown to play a critical role in the regulation of the hypothalamic-pituitary-gonadal axis, thus in turn influencing fertility and reproduction. This review examines the physiological role of kisspeptin and the kisspeptin receptor in the control of gonadotrophin and gonadal steroid hormone secretion and the implications of these findings with respect to fertility. In addition, the potential therapeutic use of kisspeptin in the treatment of reproductive disorders will be examined.

Prokineticin 2 Is a Hypothalamic Neuropeptide That Potently Inhibits Food Intake

OBJECTIVE Prokineticin 2 (PK2) is a hypothalamic neuropeptide expressed in central nervous system areas known to be involved in food intake. We therefore hypothesized that PK2 plays a role in energy homeostasis. RESEARCH DESIGN AND METHODS We investigated the effect of nutritional status on hypothalamic PK2 expression and effects of PK2 on the regulation of food intake by intracerebroventricular (ICV) injection of PK2 and anti-PK2 antibody. Subsequently, we investigated the potential mechanism of action by determining sites of neuronal activation after ICV injection of PK2, the hypothalamic site of action of PK2, and interaction between PK2 and other hypothalamic neuropeptides regulating energy homeostasis. To investigate PK2s potential as a therapeutic target, we investigated the effect of chronic administration in lean and obese mice. RESULTS Hypothalamic PK2 expression was reduced by fasting. ICV administration of PK2 to rats potently inhibited food intake, whereas anti-PK2 antibody increased food intake, suggesting that PK2 is an anorectic neuropeptide. ICV administration of PK2 increased c-fos expression in proopiomelanocortin neurons of the arcuate nucleus (ARC) of the hypothalamus. In keeping with this, PK2 administration into the ARC reduced food intake and PK2 increased the release of α-melanocyte–stimulating hormone (α-MSH) from ex vivo hypothalamic explants. In addition, ICV coadministration of the α-MSH antagonist agouti-related peptide blocked the anorexigenic effects of PK2. Chronic peripheral administration of PK2 reduced food and body weight in lean and obese mice. CONCLUSIONS This is the first report showing that PK2 has a role in appetite regulation and its anorectic effect is mediated partly via the melanocortin system.

Biology of Kisspeptins

In recent years, a substantial body of evidence has accumulated suggesting that the hypothalamic peptide hormone kisspeptin and its cognate receptor, G-protein-coupled receptor 54, play a fundamental role both as gatekeepers for the initiation of puberty and in the regulation of the hypothalamic-pituitary-gonadal axis. This review discusses the physiology of the kisspeptin signalling system and examines how findings from animal and human studies have contributed to our understanding of the pathophysiology of idiopathic hypogonadotropic hypogonadism.

Thyroid Hormone Receptor Beta in the Ventromedial Hypothalamus Is Essential for the Physiological Regulation of Food Intake and Body Weight

Summary The obesity epidemic is a significant global health issue. Improved understanding of the mechanisms that regulate appetite and body weight will provide the rationale for the design of anti-obesity therapies. Thyroid hormones play a key role in metabolic homeostasis through their interaction with thyroid hormone receptors (TRs), which function as ligand-inducible transcription factors. The TR-beta isoform (TRβ) is expressed in the ventromedial hypothalamus (VMH), a brain area important for control of energy homeostasis. Here, we report that selective knockdown of TRβ in the VMH of adult mice results in severe obesity due to hyperphagia and reduced energy expenditure. The observed increase in body weight is of a similar magnitude to murine models of the most extreme forms of monogenic obesity. These data identify TRβ in the VMH as a major physiological regulator of food intake and energy homeostasis.

Validity of very short answer versus single best answer questions for undergraduate assessment

BackgroundSingle Best Answer (SBA) questions are widely used in undergraduate and postgraduate medical examinations. Selection of the correct answer in SBA questions may be subject to cueing and therefore might not test the student’s knowledge. In contrast to this artificial construct, doctors are ultimately required to perform in a real-life setting that does not offer a list of choices. This professional competence can be tested using Short Answer Questions (SAQs), where the student writes the correct answer without prompting from the question. However, SAQs cannot easily be machine marked and are therefore not feasible as an instrument for testing a representative sample of the curriculum for a large number of candidates. We hypothesised that a novel assessment instrument consisting of very short answer (VSA) questions is a superior test of knowledge than assessment by SBA.MethodsWe conducted a prospective pilot study on one cohort of 266 medical students sitting a formative examination. All students were assessed by both a novel assessment instrument consisting of VSAs and by SBA questions. Both instruments tested the same knowledge base. Using the filter function of Microsoft Excel, the range of answers provided for each VSA question was reviewed and correct answers accepted in less than two minutes. Examination results were compared between the two methods of assessment.ResultsStudents scored more highly in all fifteen SBA questions than in the VSA question format, despite both examinations requiring the same knowledge base.ConclusionsValid assessment of undergraduate and postgraduate knowledge can be improved by the use of VSA questions. Such an approach will test nascent physician ability rather than ability to pass exams.

Beyond Weight Loss: Establishing a Postbariatric Surgery Patient Support Group—What Do Patients Want?

Purpose There are limited resources for long-term specialist follow-up after bariatric surgery. In selected centres, patients can access a postoperative support group, but there is no clear evidence to guide their delivery. Materials and Methods A retrospective study of bariatric surgery patients (n = 152) who had been discharged from specialist follow-up (mean time since surgery 5.5 years), covering weight history, physical and psychosocial comorbidities, and the need for a postoperative bariatric support group. Results Fifty-eight percent wanted a postbariatric surgery patient support group. This was not associated with operation type or the amount of weight lost or regained. However, those who wanted a support group were significantly more likely to be struggling to keep the weight off, to be unhappy with the way they look, or to be experiencing difficulties returning to work. Conclusions These data point to an unmet patient requirement for a postoperative support group that is independent of weight loss success. More research is required to ascertain how such a group should be delivered, but our data would suggest that supporting patients with weight loss maintenance, body image, and return to work is an important part of postoperative care, and these needs extend well beyond the immediate period of specialist follow-up.