TVP Christmas Lunch at The PINT SHOP Cambridge 9th December ‘15
By Helen Westby, Disease Model Core
This years TVP Group’s Christmas meal took place on 9th December at The PINT SHOP in the centre of Cambridge. The keenest of attendees were already “parked” at their tables as the rest of us wondered in at around 12.30pm.
We were welcomed in by very friendly and obliging staff, and escorted upstairs to the dining area. Tables neatly arranged, we all settled in quickly and took advantage of the extensive drinks menu! This being the PINT SHOP, many of the party decided it’d be rude not to partake in a pint of beer. That said, there were many other beverages on offer, including a myriad of Gins and Whiskeys.
The first course was served in good time, and was enjoyed by the merry throng. Indeed all three courses appeared to go down well? And everyone I spoke to seem to give it a firm “thumbs up”.
In general it was a very relaxed affair; giving everyone the opportunity to chat to people they don’t always see on a day to day basis. However, this being a Christmas Party, there was bound to be a few High Jinx going on?? This years prize has to go to the members of the DMC, who were kept entertained by a simple Christmas Cracker Novelty! It came in the shape of a yellow plastic jumping “Bug”, nicknamed Percy Pineapple. Flicking this creature around the table, attempting to land it in an unsuspecting victims glass, kept this bunch amused for ages. How said bug ended up on our hosts shoulder however, is anyone’s guess? 😉
All in all it was a thoroughly enjoyable and entertaining afternoon.
Finally, I’m sure everyone would like to extend their Thanks to Toni, Katie and Agnes for arranging this event, and to the efficient and hard working staff at The PINT SHOP.
Professor Toni Vidal-Puig was interviewed about the potential use of stem cells to increase brown adipose tissue as therapeutical strategy to fight against obesity and associated metabolic disorders
“Brown adipose tissue thermogenic capacity is regulated by elovl6”.
Chong Yew Tan, Sam Virtue et al Cell Reports (TVPLab)
Our paper shows that the development of obesity depends not only on the amount but also on the type of energy available. We showed that the chain length of the fatty acids determines the intensity of the thermogenic response by enabling the mitochondria from the brown adipose tissue to be more efficient at burning the excess of fat. This helped to prevent obesity and its associated complications.
Sam Virtue and Chong Yew Tan, members of the Vidal-Puig Lab, have shown that the Elovl6 enzyme, whose function is to elongate fatty acids from 16 carbons (C16) to 18 carbons (C18), is up regulated in brown and white adipose tissues when exposed to cold and that this helps to optimise heat production and energy dissipation.
Using a mouse where Elovl 6 was genetically eliminated, we observed that, when exposed to cold, lack of this enzyme prevented increasing C18 fatty acids levels clearly indicating the relevance of Elovl6. Interestingly these mice also had impaired energy dissipation and were more susceptible to become obese, diabetic and had enlarged fatty liver particularly when they were getting older or when fed a diet rich in calories while living at high temperatures. This combination of risk factors seems to be very relevant nowadays when the population is ageing rapidly, when high calorie junk diets are widely available and many people live a comfortable life in warm houses.
An important question is how changes in fatty acid chain length can affect the function of mitochondria and heat production. One possibility relates to direct changes in the membrane lipid composition of the mitochondria, which we found to be enriched in C18 fatty acids.
However a non excluding alternative is that C18 fatty acids may modify and regulate proteins that control the activity of the mitochondria. We have recently shown in a recent paper in Nature (http://www.nature.com/nature/journal/vaop/ncurrent/full/nature14601.htmland) that C18 can modify the transferring receptor and improve mitochondria function in flies and cells. In our current paper we show that this mechanism is also relevant in mice, further supporting the concept that chain length of fatty acids is an important regulator of signalling events capable of controlling energy balance.
The implication of our study goes beyond the conceptual advance linking chain length of fatty acids to mitochondria function. In fact it is conceivable that dietary supplementation of C18 fatty acids may provide health benefits in those more vulnerable, the ageing and metabolically compromised population and/or that may amplify potential benefits derived from changes in ambient temperature.
This report was published in Cell reports on the 25/11/2015.
Congratulations to Dr Andrew Whittle on your new Nature publication in collaboration with Prof Hideaki Bujo’s lab
Read the full paper here
The EMBO Leadership and Management Course sponsored by MRC in Cambridge
This is an excellent course focused on the leadership challenges and managerial problems we face in research intensive academic institutions. Conducted over four days by two experts from hfp Consulting, Thomas Frick and Jorg Stange, the course covered a wide range of areas in enough depth to be useful. During these four days senior and less senior investigators shared a good mix of experiences and perspectives that were very enriching. In my opinion the course is highly recommendable and has an excellent value. Also I would recommend it to very senior academics, particularly to those who feel they know everything. It is a good and enjoyable learning experience that can make a difference to your institutions.
Congratulations Dr Vivian Peirce
A huge congratulations to Vivian Peirce, PhD student in the TVPLab for the last 4 years who has recently defended her thesis entitled “Regulation of adipose tissue function by bone morphogenic protein 8b” . Vivian’s PhD was focused on brown and white adipose tissue. By exploring the role of bone morphogenic protein 8b (Bmp8b) as a regulator of thermogenic response in both these depots, she developed skills in several domains from animal physiology to cell and molecular biology and produced very exciting data. We will miss her and wish this dynamic and creative young scientist all the best and good luck in her future career.
Fatty Acid and Glucose Sensors in Hepatic Lipid Metabolism: Implications in NAFLD
Michele Vacca, MD, PhD, Michael Allison, MD, PhD,Julian L. Griffin, PhD, Antonio Vidal-Puig, MD, PhD
Read Full Review Here (PDF)
The TVPLab from the Institute of Metabolic Science sponsors the Cherry Hinton Lions Under 12 Football Club
New research into child activity rates in the UK has found that over 77% of children are doing no more than four hours of out of school exercise each week. The TVPLab and the Institute of Metabolic Science supports the commitment of the MRC, BHF and Diabetes UK to inspire millions of people to eat better and get active. Here is our direct contribution in our local community in Cambridge.
First game first win of the season for the Cherry Hinton Lions blue under 12 football team sponsored by the TVPLab
22-0 was a great start…….However do not hold your breath, the competition is tough and it may not be so easy next time!
If you want to sponsor our football team, please do not hesitate….contact us…there is still space on the back of our shirt….
Prof Toni Vidal-Puig awarded the FEBS National Lecture 2015
Prof Toni Vidal-Puig has been awarded the FEBS National Lecturer 2015. The FEBS National Lecturers were established to commemorate the 40th anniversary of the Federation of European Biochemical Societies. These FEBS National Lecturers are intended as Plenary Lectures. The Lecturer should be a distinguished scientist with international reputation. An application proposing a maximum of two candidates for the FEBS National Lecturer, including short Curricula Vitae and with full details of the event, shall be sent to the FEBS Congress Counsellor. The deadline for applications is 1 October of the preceding year. The application is evaluated by the Executive Committee members of FEBS and awarded within 2 months of receipt of the application.
What is brown fat?
Get beneath the skin on this physiological secret – fat that makes you thin
The Royal Academy of Medicine of the Pricipado de Asturias has awarded Prof. Toni Vidal Puig the 2015 Hippocrates International Award for research in human nutrition. This prize is awarded to scientists dedicated to pursuing research questions in the areas of human nutrition and metabolism. The prize panel recognized the TVP lab’s contributions to unravelling molecular mechanisms of metabolism and energy expenditure. Read more here: http://www.rampra.org/
Elovl6 in the control of mitochondrial function
In collaboration with the Teleman lab (Heidelberg) the Vidal-Puig laboratory has identified a mechanism where by production of stearate by the enzyme Elovl6 is necessary to maintain appropriate mitochondrial function. Cells grown in media lacking stearate exhibited low mitochondrial respiration and fragmented mitochondria.
Stearate acts to prevent mitochondrial fragmentation by blocking Transferrin receptor 1 activity via stearoylation. This in turn prevents the phosphorylation and ubiquitination of mitofusin 2. Supplementing the diet of fly models of Parkinson’s disease was able to improve the life span of these models, suggesting stearate supplementation may be protective for diseases caused by mitochondrial defects.
EAS Advanced in Cardiometabolic Phenotyping in Rodents, Cambridge, UK
Scientists from the University of Cambridge Biomedical Campus recently hosted the 2nd EAS Advanced Course in Cardiometabolic Phenotyping in Rodents. This 3-day course combines the state of the art facilities and expertise within the Disease Model Core at the WellcomeTrust-MRC Institute of Metabolic Science and the BHF Cardiovascular Centre. By integrating the expertise of these two specialized phenotyping centres, it provides a unique opportunity to learn about many of the skills required for in depth cardiometabolic phenotyping in small animals.
The 32 participants, selected from centres across Europe, were treated to a programme of lectures, phenotyping demonstrations and data analysis sessions. A further 1-day workshop at the Sanger/EBI focused on mouse genetics, genetic engineering and informatics resources, highlighting the great opportunities provided by recent advances in genetic engineering purpose-made mouse models. Participants particularly appreciated the mixture of hands-on experience, combined with opportunities to ask detailed questions on how the techniques demonstrated should be used to suit their own research priorities.
The course was sponsored by the European Atherosclerosis Society, British Heart Foundation and TSE systems, with organisation led by Prof Toni Vidal-Puig, Director of the MRC Metabolic Diseases Unit Disease Model Core.
Vivian Peirce and Stefania Carobbio recently had the opportunity to write a review for Nature about brown, white, and beige adipose tissue. The review focuses on recent advances in adipose tissue biology, with a view to target adipose tissue to treat metabolic disease in humans. To find out how manipulating white and brown fat could ameliorate metabolic dysfunction, read more here.
Until recently, our body fat, the adipose organ, was thought to be composed by white adipose tissue, which has been described merely as a passive storage organ for excess calories, and of brown adipose tissue, described to be present in infants, which functions primarily to consume fat to produce heat to maintain core body temperature. Read more here.
Sanger Institute Blog by Dr Stefania Carobbio
From clinical studies and animal models, scientists have noticed that some obese individuals can maintain a remarkable capacity to store fat before experiencing adverse metabolic effects associated with obesity, such as insulin resistance and Type 2 diabetes. It seems that the adipose tissue of these people has developed adaptive mechanisms that allow it to preserve its functionality while adjusting its biochemical features to maintain its biophysical characteristics. Read more here.
Sanger Institute Blog by Dr Stefania Carobbio
Congratulations from everyone in the TVP Lab. More
TVP Lab members give presentations and posters at 1st ICAN conference series in Cardiometabolic Disease
Members of the TVP lab recently attended the 1st ICAN conference series in Cardiometabolic Disease in Paris. Vanessa Pellegrinelli was selected to give a presentation, and Camilla Ingvorsen, Guillaume Bidault, and Vivian Peirce were selected to present posters. Vivian Peirce was a joint-winner of Young Investigator poster award.
Cherry Hinton Lions Under 10s Blue Football Club sponsored by IMS
Obesity is one of the most important biomedical problems in our society and also one of the most frustrating to tackle. For this reason, the recent identification of functional brown fat in adult humans has made the obesity research community very excited. Read more here.
Sanger Institute Blog by Dr Stefania Carobbio
As part of the Cambridge-National University of Singapore link up, Dr Cheryl Yeo, a Post Doc working with Dr Sue-Anne Toh and Professor Shyong Tai, visited the TVP lab as part of acollaboration to study adipose tissue inflammation and function.
Sam Virtue & Cheryl Yeo
A huge congratulations to Chong Yew Tan and Crystal Mok who have both recently passed their PhD vivas with flying colours. Chong and Crystal started their PhDs in 2009 and have both produced exciting results. Chong’s PhD was focussed on the role of fatty acid chain length and metabolic disease while Crystal has worked on the interaction of insulin signalling and inflammation in adipose tissue macrophages. Both Chong and Crystal are currently continuing their research in the TVP laboratory in order to complete publications based on their PhD work.
We are also glad to announce that Iris Schmitt successfully passed her PhD oral exam in August. Iris’ research was mostly focused on the role of etherlipids in adipose tissue expansion. The TVP Lab wish to congratulate Iris for such an achievement and we wish her all the best in her future career.
Congratulations to Andy Whittle
Who has been awared an EMBO long-term fellowship to work with Dr Luis de Lecea at Stanford University, San Francisco. Andy started at the MRL as a PhD student then a postdoc in the TVP Lab using murine metabolic phenotyping techniques to study the physiological regulation of thermogenesis and energy balance. He aims to use this 2-year fellowship, which starts in October to develop skills in murine neuroscience and understand the role of metabolically important neuronal circuits in the control of brown adipose tissue, particularly in the context of thermogenic responses to nutritional challenges. The TVP Lab wish Andy the best of luck in with his new position and life in the US!
A farewell note from Andy:
“After 7 years in the TVP lab I have made many good friends both in the lab and the wider department at the IMS. My time at Cambridge has been challenging (in the best of ways), exciting, filled with interesting twists and turns in the path my research has taken and above all else, thoroughly enjoyable. I am now moving to the lab of Luis de Lecea at Stanford University to continue to study the neuronal circuits that regulate energy expenditure and brown adipose tissue thermogenesis, with the support of an EMBO long-term fellowship. I look forward to all the new challenges and opportunities this chapter will bring, but I am also sad to leave behind such a happy and fulfilling environment to work in. Thank you to all the people who have made my time at Cambridge so special and a special thank you to Toni, for being willing to mentor the naïve student that arrived 7 years ago. I will be forever indebted. I’ll make sure I keep in touch and look forward to seeing you all again soon!”
Systems biology is an emerging field with great potential to advance the study of metabolic syndrome. Matej Oresic and Toni Vidal Puig are the editors of the recently released book A Systems Biology Approach to Study Metabolic Syndrome. This book is a practical guide to the research community, focusing on how the latest systems biology technologies and mathematical modelling approaches can be used to tackle specific pathophysiological aspects of metabolic syndrome.
Prof Toni Vidal-Puig presents Summer Clinical Research Seminar at Toho University “Sakura” Medical Center, Tokyo, Japan.
In light of the recently published review entitled “Pharmacological strategies for targeting BAT thermogenesis” in Trends in Pharmacological Sciences, Toni was interviewed by the journal editor to explain why brown adipose tissue thermogenesis (BAT) is an emerging target for weight loss. In contrast to white adipose tissue, which stores energy, BAT burns energy off as heat to maintain body temperature, at least in rodents. Our understanding of BAT function in rodents has been made clinically relevant by the recent discovery of BAT in humans. In the context of obesity, activating BAT could reverse the state of positive energy balance responsible for weight-gain, so that instead energy dissipation dominates, creating a negative energy balance that the body cannot compensate for adequately by increasing food consumption. This strategy has a distinct advantage over weight-loss strategies that limit energy intake, for example dieting, because the body is able to compensate for decreased energy intake by decreasing energy expenditure. BAT activity is primarily regulated by the sympathetic nervous system. However, researchers are attempting to identify molecules unrelated to sympathetic tone that can increase BAT mass or activate BAT in order to avoid the undesirable side-effects of drugs that increase sympathetic tone non-selectively. Additionally, beige cells – brown-like cells capable of thermogenesis that appear dispersed in white adipose tissue – are receiving increasing amounts of attention, as the field debates whether beige cells or canonical brown adipocytes are the most relevant cell-type to energy balance in humans.
Read the review here
The PhD students at the MRL have an annual student symposium, at which they give a short presentation or present a poster. This year Vivian Peirce presented a poster entitled “Investigating the Central Mechanisms Regulating Thermogenesis,” and won the best poster prize at the afternoon poster session.
In research published in the journal Cell, studies led by Professor Vidal-Puig show the protein BMP8b stimulates the activity of brown fat by acting in both the brain as well as in brown fat itself. BMP8b was found to increase the nerve activity to brown fat and also sensitize the brown fat cells to nervous stimulation, maximizing their metabolic activity. The work was subsequently featured in New Scientist, where Dr Andrew Whittle explains the potential application of BMP8b for increasing energy expenditure and reducing body weight.
Obesity is a growing problem in society. Brown fat, which in the past was thought to be present only in human infants, has recently been discovered in adults as well. Brown fat consumes calories to produce heat to maintain core body temperature. Thanks to central heating, we rarely expose ourselves to the cold and do not routinely use brown fat in this capacity. However, pharmacological stimulation of brown fat could provide a new avenue for obesity treatment with few side-effects. Read more
The risk of overall mortality increases with increasing BMI. However, a recent study controversially suggests that, while obese patients (BMI >30) have an increased overall mortality risk, moderately overweight patients (BMI 25-30) have a decreased overall mortality risk compared to patients with a normal BMI (BMI 18-25). These results ought to be treated with caution due to potential confounding factors and biases in the study. Even then, a decreased mortality risk does not mean that moderately overweight patients are actually healthier. Taking cancer as an example, moderately overweight patients with cancer may have a better chance of survival than patients of normal weight due to increased caloric reserves stored in fat. It is possible that though increased BMI is associated with increased disease risk, when a patient is ill, greater fat reserves due to being moderately overweight actually increase the likelihood survival. Furthermore, when defining obesity, information about body composition must be considered – for example, elite athletes with a large amount muscle mass may be classified as obese according to their BMI. Finally, how much fat a person has may not be as important as how well their fat—both white and brown—is functioning. Read more
Obesity is a massive worldwide health problem, associated with cardiometabolic complications. For the first time in history it is quite likely that the current generation may live shorter lives than their ancestors.
Toni Vidal-Puig joins The Wellcome Trust Sanger Institute as Associate Faculty Member
Toni will spend part of his time at the Institute, bringing complementary insights and expertise of new areas of research to the knowledge and resources of the Sanger Institute and thus broaden the portfolio of scientific inquiry. Toni will be working with the Institute using mouse models to understand genes that affect energy balance and mechanisms responsible for the secondary complications of obesity.
The balance between energy expenditure and energy intake is vital to maintaining stable body weight. Therefore, understanding the processes that contribute to energy expenditure is vital in order to interpret the results of studies into the causes and consequences of obesity.
While most mammals expend energy by exercising more, by shivering and by activating heat production in brown fat (a process called non-shivering thermogenesis), the relative importance of each of these is not well understood.
In research published in the journal Cell Metabolism, studies led by Dr Sam Virtue and Professor Vidal-Puig at the University of Cambridge Metabolic Research Laboratories Disease Model Core demonstrate that how much a mouse moves does not appear to affect how much energy it expends at temperatures below its thermal neutral zone (the environmental temperature at which an animal does not need to make heat in order to maintain body temperature). For mice, the thermal neutral zone is 30˚C, and the study shows that, below this temperature, increased energy expenditure from activity may be compensated for by reduced heat production from other sources such as non-shivering thermogenesis in brown adipose tissue.
As most studies take place below 30˚C, this has important implications for interpreting the results of studies into why some mice are lean or obese and, ultimately, understanding human obesity.
The study is published in the following article:
One of the most important public health issues is obesity. The last 50 years have seen an obesity epidemic spreading uncontrollably on the planet. The problems of obesity are not limited to mechanical problems caused by excess weight, or psychological problems arising from the perception and stigmatization of the obese patient. The obese patient dies due to their greater tendency to develop diabetes, atherosclerosis, myocardial infarction, stroke or cancer. If left unchecked the first epidemic of obesity is to be expected as a second epidemic devastating tsunami of cardiometabolic diseases and cancer in a population more vulnerable because of their age. And the problem is not just the human suffering it produces but also the economic implications on health systems financially precarious. With this bleak outlook it is essential to reanalyze the situation and set clear objectives. Read more
Following the EAS Advanced Course IV: Murine genetics and cardiometabolic phenotyping in Cambridge this July, we are very pleased that the course was deemed to be a success. 97% rated the educational value of the Course to be high and 98% rated the course to be applicable to their own research. Further feeback can be found here.
Dr Andrew Whittle presents at the Joint FEPS and Spanish Physiological Society Scientific Congress
On September 10th 21012 Dr Andrew Whittle attended the Joint FEPS and Spanish Physiological Society Scientific Congress in Santiago de Compostela, Spain. He delivered a talk discussing the concept of “BATokines” – biologically active molecules produced by brown adipose tissue that have effects on metabolic processes in other organs. The meeting was attended by leading researchers in the fields of physiology, endocrinology, metabolism and brown fat.
Dr Sam Virtue presents at European Neuroendocrinology Society meeting
Dr Sam Virtue recently presented at the prestigious European Neuroendocrinology Society meeting in Vienna. Sam’s talk was focussed on metabolomics in endocrinology and was based on the past 9 years of experience in the TVP lab in the field of lipodomics. The purpose of the talk was to discuss how biologists without systems biology experience can work with groups specialising in the fields of metabolomics to design appropriate experiments and extract the maximum value from their data sets.
Dr Sam Virtue presents to the York Branch of Diabetes UK
As part of the TVP laboratory’s commitment to public engagement in science, Dr Sam Virtue (pictured right with Margaret Davies of Diabetes UK Organising Committee) recently gave a talk to the York Branch of Diabetes UK. Diabetes UK is the leading independent charity raising money for the study of diabetes in the UK. Over twenty people who are involved in fundraising for Diabetes UK attended the tak which focussed on the causes of type II diabetes and potential new treatments based on the work of the TVP laboratory in the field of brown adipose tissue.
Sam would like to thank the York Branch of Diabetes UK for inviting him to speak.
The link between obesity and type 2 diabetes is clear on an epidemiological level, however the mechanism linking these two common disorders is not well defined. One hypothesis linking obesity to type 2 diabetes is the adipose tissue expandability hypothesis. The adipose tissue expandability hypothesis states that a failure in the capacity for adipose tissue expansion, rather than obesity per se is the key factor linking positive energy balance and type 2 diabetes. All individuals possess a maximum capacity for adipose expansion which is determined by both genetic and environmental factors. Once the adipose tissue expansion limit is reached, adipose tissue ceases to store energy efficiently and lipids begin to accumulate in other tissues. Ectopic lipid accumulation in non-adipocyte cells causes lipotoxic insults including insulin resistance, apoptosis and inflammation.
This article discusses the links between adipokines, inflammation, adipose tissue expandability and lipotoxicity. Finally, we will discuss how considering the concept of allostasis may enable a better understanding of how diabetes develops and allow the rational design of new anti diabetic treatments.