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Despite being in the age of information technology, with a wealth of molecular data at our fingertips, relatively simple clinical parameters such as BMI and fasting glucose are used to diagnose complex metabolic disorders. These clinical markers have stood the test of time and are affordable. However, given that many patients taking top-selling drugs fail to benefit from their prescriptions (Schork, 2015xSchork, N.J. Nature. 2015; 520: 609–611Crossref | PubMed | Scopus (152)See all ReferencesSchork, 2015), we are sharply reminded that a “one size fits most” approach may not always be effective for diagnosing and treating heterogeneous diseases such as the metabolic syndrome. The need for individualized therapies has prompted various countries, including the United States, the United Kingdom, and China, to launch “Precision Medicine” initiatives, recognizing the need to collect and analyze big data from the population at large to ultimately benefit the health of sub-populations and individuals. In the United States, this has paved the way to an all-inclusive research program led by the NIH, “All of Us,” tapping into the rich diversity of the United States population, which promises to collect and analyze lifestyle, environmental, and biological data from one million volunteers in order to cover a wide array of health conditions.The hope of understanding and treating the patient as an individual rather than as part of a generic class has started to materialize. Given their tractability, rare monogenic diseases, such as the extreme hyperphagia and obesity of two patients with proopiomelanocortin deficiency being treated with a melanocortin-4 receptor agonist (Kuhnen et al., 2016xKuhnen, P., Clement, K., Wiegand, S., Blankenstein, O., Gottesdiener, K., Martini, L.L., Mai, K., Blume-Peytavi, U., Gruters, A., and Krude, H. N. Engl. J. Med. 2016; 375: 240–246Crossref | PubMed | Scopus (33)See all ReferencesKuhnen et al., 2016), have seen success stories. Long-term strategies will be aimed at deciphering more complex and heterogeneous pathologies, ranging from cancer to metabolic disorders. In 2011, the National Research Council of the United States called for a “knowledge network,” which layers and connects complex factors, ultimately building a new “taxonomy of disease” from which a patient can be diagnosed through the integration of omics data. The omics include exposomes (exposure-omics), metabolomes, genomes, epigenomes, and microbiomes (NRC, 2011xToward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease. National Research Council. See all ReferencesNRC, 2011). In this Special Issue, we introduce the concept of “Precision Metabolism” and review our quiver of complex factors that need to be integrated to individually target metabolic health and disease.Maggi and colleagues kick off the issue with one of the most basic differences between individuals: sex. In their essay they argue that, with evolutionary pressure driving sex divergence and positive selection on females to adapt their energy metabolism to their reproductive needs, sex differences are intricately weaved into the pathology of metabolic disorders. Focusing on immune-metabolic crosstalk, Elinav and colleagues tackle the complex dynamic equilibrium between diet, host genome, gut microbome, and the immune response from conception through birth to old age. With the march of time, an individual’s metabolism shifts, as does his or her immune state; they propose the intriguing possibility of harnessing the immune system as a means of personalized treatment of some metabolic disorders. Leulier and colleagues review diet, host physiology, and microbiota within an integrative framework from model organisms to humans, and propose a theoretical concept, the nutritional geometry framework, for personalized diet optimization. This concept is applied in a research article in this issue, in which Piper and colleagues (2017)xPiper, M.D., Soultoukis, G., Blanc, E., Mesaros, A., Herbert, S., Juricic, P., He, X., Atanassov, I., Salmonowicz, H., Yang, M. et al. Cell Metab. 2017; 25: 610–621Abstract | Full Text | Full Text PDF | PubMed | Scopus (9)See all References)Piper and colleagues (2017) use the genomic information of an organism to define its dietary amino acid requirements, and show that exome-based designer diets optimize fitness in flies and mice.Although one would intuitively think that understanding the underlying genetic basis for obesity would be helpful, Loos and Janssens take a sobering look at where we are in understanding the polygenic basis of obesity risk. Though we have nearly 200 common genetic variants associated with obesity, we are still coming up short in our predictive capacity compared to traditional parameters, such as family history and childhood obesity. As we are now realizing, however, epigenetics provides an additional layer of complexity on top of our genetics, as our “non-genetic molecular legacy of prior environmental exposures.” Two Perspectives, one by Rando and colleagues, and one by Patti and colleagues, review the complex links between metabolism and epigenetic modifications and multigenerational disease links transmitted through germ cells. Nielsen and colleagues close the issue from a systems perspective, bringing into focus the unprecedented availability of big data for integrative analysis, and take us back to the individual, looking at the immense value of N-of-1 clinical trials with large cohorts.Sixteen years since the publication of the first draft of the human genome, we are watching the arrow of precision medicine fly toward the bull’s-eye of metabolic health.

Last year we, the editors of Cell Metabolism, started our “Rosie project,” where we asked women scientists to share some of the defining stories of their careers and for their advice for the next generations of researchers. We were inspired by the World War II poster, Rosie the Riveter, which we featured on the May 2015 Cell Metabolism cover to debut the “Women in Metabolism” series of “Voices.” Throughout the year, we published 41 Voices in three installments from scientists all over the globe. The response of our readers has been so overwhelmingly positive that we decided to continue and extend the Rosie series.View Large Image | View Hi-Res Image | Download PowerPoint SlideSo welcome now to the second act of the Rosie project. For starters, we have broadened the series to include men! For the first 2016 Rosie series, we are partnering with our Cell Press colleagues to highlight an upcoming LabLinks meeting on “The Gender of Science and the Science of Gender” to be held Thursday, May 19, 2016 at the Koch Institute for Integrative Cancer Research at MIT in Massachusetts, USA. To provide some background, LabLinks are a Cell Press tradition we are particularly proud of. They are free Cell Press-sponsored meetings, held in various cities around the world, which, for one day, bring together scientists with a shared interest. Time and time again, we have been told that, though most of the speakers and attendees are from the same city, they do not often have such an opportunity to come together and discuss topics close to their hearts. Invariably, fruitful discussions have led to productive collaborations, exciting research, and new vistas. Since the first LabLinks on microbial immunity a decade ago, we have covered a diverse portfolio of topics in the life sciences, ranging from chromatin and DNA repair to synthetic biology via metabolic disease. This is, however, the first time that we are tackling a non-traditional topic combining social and biological sciences as well as policy.The LabLinks on gender and science is the brainchild of one of us, Nicole, while Liz, the author and curator of the Female Scientist blog, was a natural partner to co-spearhead the project. Together with other colleagues across Cell Press and Elsevier, and in a first-time partnership with the Massachusetts chapter of the Association of Women in Science (Mass AWIS), we are excited to be able to present this meeting exploring both the social issues of gender diversity in science and the biology of gender. The goal of the meeting is to keep the conversation about women in science going. It’s clear the conversation started a while ago; we now need to move beyond the beaten tracks to recognize and capitalize on gender diversity in a smart and empowering manner for both women and men.Reflecting the meeting’s duality, Londa Schiebinger, from Stanford, will deliver the keynote lecture about gendered innovations—the true incorporation of gender as a variable in scientific research and technology development, from using crash-test dummies with the body composition of both men and women to including sufficient women or men in clinical trials—while the second keynote speaker, Catherine Dulac, from Harvard, will talk about the neurobiology of human behavior—does our biology drive men and women to think and behave differently? The speaker roster, composed of an 85% ratio of women speakers, which is reflective of the customary number of male speakers at scientific conferences, includes Evelyn Murphy speaking on wage equality and David Clapham speaking on male contraception strategies. The LabLinks will include a panel discussion on how diversity can be achieved in a meritocracy.For this Cell Metabolism Rosie series, we invited the LabLinks speakers, as well as Sangeeta Bhatia and Harvey Lodish from MIT, for their reflections on women scientists. Reading the authentic accounts of these rock stars of science, we are particularly struck by their passion and perseverance in pursuing their dreams in advancing science and society and by the incontrovertible importance of mentorship. A culture of inclusion not only provides a diverse “highly educated, creative, innovative, and motivated” talent pool, it is “essential for both individual success and to provide the creative spark …” Besides fostering meritocracy, diversity improves the financial bottom line of institutions and countries.Our collective aim is to make science a better place so that we can be a “scientist” first and foremost, not a “woman scientist” or a “man scientist” or have any other similar qualifier before our professional job description. We hope you enjoy this series of Voices as a preview of the May 19th event in Cambridge, and that you will continue to support each other as fellow STEM researchers. We can do it!

Leave all the afternoon for exercise and recreation, which are as necessary as reading. I will rather say more necessary because health is worth more than learning.—Thomas JeffersonTwo years ago, we successfully brought together leaders in the exercise field, including physiologists, clinicians, and molecular biologists, to promote cross-pollination of ideas for the first Cell Symposium on Exercise Metabolism in Amsterdam. When the time came to decide whether or not to repeat the meeting, the “yes” vote was unanimous. We again teamed up with Drs. Juleen Zierath and John Hawley for the second running of the Exercise Metabolism Cell Symposium, this time in Sweden, which has a long tradition in exercise physiology. This Special Issue of Cell Metabolism on the theme of exercise sets the stage for our upcoming symposium in May, starting with a unique cover featuring many of the Cell Symposium speakers and Cell Metabolism editors getting their heart rates up. Besides our Speaker and Editor Voices series, which blends personal stories and research inspiration, you will find a Crosstalk and a Perspective, as well as Reviews and research articles, on exercise.Although we all know that exercise is good for us, promotes healthy aging, improves cognitive function, and staves off a wide range of diseases, the WHO reports that physical inactivity ranks as the fourth leading risk factor for global mortality (http://www.who.int/dietphysicalactivity/pa/en/). In their Crosstalk opinion article, Gibala and Hawley underscore that lack of time is one of the main reasons for delaying going to the gym and discuss the idea that high-intensity interval training might be an effective way of addressing this conundrum. However, despite interval training gaining in popularity, the most effective protocol is still somewhat unclear, as are the underlying molecular mechanisms.In case you are wondering what exercise physiology is, Gabriel and Zierath define it as the “science of studying limits: the limits of elite performance, the limits of the health benefits of exercise, or the limits/barriers to achieving increased population-wide participation in exercise.” Their Perspective highlights how early investigations on the physiological limits of performance have set the stage for modern day exercise scientists to start unraveling the molecular mechanisms of exercise. Cardiac adaptation and fuel selection are, of course, important determinants of performance. Leinwand and colleagues compare an athlete’s physiological heart growth to the pathological hypertrophy observed with hypertension or ischemic heart disease, illustrating how exercise pathways can antagonize pathological pathways. Goodpaster and Sparks argue in their overview of metabolic flexibility in fuel selection that, while targeting metabolic inflexibility in diabetes and obesity is an attractive therapeutic option, “any pharmacologic strategy purporting to mimic exercise would need to impact metabolic flexibility and also induce increases in energy expenditure and demand similar to exercise. This should prove to be challenging, if not impossible.”As the molecular mechanisms underlying exercise emerge, the controversial topic of “exercise in a pill” often comes up. Contrary to Goodpaster’s view on exercise mimetics, a recent Perspective in our journal by Fan and Evans argues that exercise mimetics are already here and discusses their effects on health and as performance-enhancing drugs (Fan and Evans, 2017xFan, W. and Evans, R.M. Cell Metab. 2017; 25: 242–247Abstract | Full Text | Full Text PDF | PubMed | Scopus (3)See all ReferencesFan and Evans, 2017). While it is unlikely that targeting a single pathway would recapitulate the pleiotropic effects of exercise, PPARβ/δ and AMPK have been identified as promising candidates to boost the exercise response. In this issue, the Holloszy group details a two-step process through which PPARβ/δ mediates the adaptive skeletal muscle response to endurance exercise, with an initial early mitochondria maintenance phase, followed by long-term increased mitochondrial biogenesis. Taking advantage of the fact that PPARβ/δ can be pharmacologically targeted, the Evans group shows that PPARβ/δ plays a crucial role in glucose sparing and delays the onset of “hitting the wall,” with agonist-treated mice extending their running time by over 100 min. In turn, Miller and colleagues shed new light on tissue specificity of AMPK by employing a new small-molecule activator of AMPK, which results in a re-wiring of the muscle transcriptome and rapid lowering of glucose levels, independently of AMPK activation in the liver.As the field of exercise makes strides forward, now, more than ever, we need to keep the momentum of exercise research going to better our health. On the heels of the 121st Boston marathon, highlighting endurance, willpower, and perseverance, including the spectacular participation of Kathrine Switzer, the first woman to officially run the Boston Marathon 50 years ago, we could not agree more with Ruth Loos that “the world is a better place after a run.”