Transient early food restriction leads to hypothalamic changes in the long‐lived crowded litter female mice

Transient nutrient restriction in the 3 weeks between birth and weaning (producing “crowded litter” or CL mice) leads to a significant increase in lifespan and is associated with permanent changes in energy homeostasis, leptin, and insulin sensitivity. Here, we show this brief period of early food restriction leads to permanent modulation of the arcuate nucleus of the hypothalamus (ARH), markedly increasing formation of both orexigenic agouti‐related peptide (AgRP) and anorexigenic proopiomelanocortin (POMC) projections to the paraventricular nucleus of the hypothalamus (PVH). An additional 4 weeks of caloric restriction, after weaning, does not further intensify the formation of AgRP and POMC projections. Acute leptin stimulation of 12‐month‐old mice leads to a stronger increase in the levels of hypothalamic pStat3 and cFos activity in CL mice than in controls, suggesting that preweaning food restriction leads to long‐lasting enhancement of leptin signaling. In contrast, FoxO1 nuclear exclusion in response to insulin is equivalent in young adult CL and control mice, suggesting that hypothalamic insulin signaling is not modulated by the crowded litter intervention. Markers of hypothalamic reactive gliosis associated with aging, such as Iba1‐positive microglia and GFAP‐positive astrocytes, are significantly reduced in CL mice as compared to controls at 12 and 22 months of age. Lastly, age‐associated overproduction of TNF‐α in microglial cells is reduced in CL mice than in age‐matched controls. Together, these results suggest that transient early life nutrient deprivation leads to long‐term hypothalamic changes which may contribute to the longevity of CL mice.e12379Transient nutrient restriction in the 3 weeks between birth and weaning (producing “crowded litter” or CL mice) leads to long‐term hypothalamic changes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111266/1/phy212379.pd

Foodloose in Washtenaw: A Foodie's Guide to Washtenaw County

The idea for this project came from the book Footloose in Washtenaw: A Walkers' Guide to Ann Arbor and Washtenaw County (1976) and Footloose in Washtenaw: A Revised and Expanded Walkers' Guide to Washtenaw County (1990). Both editions were written by Ruth Kraut and edited by Keith Taylor. These earlier books provide self-guided walking tours of the county, sometimes trails and other times sidewalks. The current book is intended to be the food version; hence food instead of foot. The idea is to capture the 2017-2018 Washtenaw County, Michigan local food community in the form of self-guided tours. These tours are curated with the hope of encouraging those not explicitly connected to the food community to get to know the County’s food system more intimately and to become involved, perhaps by volunteering at one of the many sites described. This project attempts to weave the multitude of connections that abound between farmers, restaurants, retailers, and other members of the Washtenaw County local food community into tours that allow for the understanding of the larger patterns at play. We encourage asking questions about geography, social networks, shared experiences, and more that might reveal what makes this local food community so unique and worthy of celebration. Then, we can begin to ask what is missing from the community, or what could improve it? These tours are based on simple connections, such as geographical proximity, themes, or simply following a flow of food. Many intricate inter-relationships exist that have not been included in this book and you are invited to discover for yourself some of these intricacies and uncover your own connections. There are biases of this book that are not entirely representative of the local food community. Some of the most apparent biases include how this book has a focus on vegetarian as well as organic, pesticide-free, and biodynamic food ventures. The information for this book was gathered through interviews that were traveled to by bicycle, bus, and the occasional car ride. This limited the scope of the project to within county boundaries. It is unfortunate that some folks who engage with our local food community were not included because they are not geographically located within Washtenaw County; nonetheless, their work is still extremely important to us. We hope that future editions will capture this expanding food community. Additionally, some of the tours in this book involve spending money at some point, in some way. It is important to recognize that it might not be possible (or wise) for some tour-goers to purchase something at every stop on a tour. For this reason, some of the tours, such as Tour de Farm and Markets, do not require spending money to have an experience. However, people who grow, process, cook, and distribute our food should have their time and effort honored with compensation. Although, this compensation does not necessarily have to be money. Money is, of course, the most convenient method of transaction, but only because we have made it so. We can, in fact we once did, exchange goods and/or services without using money. Humans have so much more to offer than greenbacks or plastic. We have skills, we have experience, we have time, and we have the ability to reciprocate creatively. This book encourages you to find a way to exchange your skills with someone who has food skills, in order to use your actions, not your money. In doing so, you will be fostering a meaningful connection with someone in your community as well as the food you eat. As Frida Kahlo once said, “Nothing is absolute, everything changes, everything moves, everything revolutionizes, all flies and goes.” This flux exists within all local food systems. A farm, store, or restaurant featured in the book will close and others will open; some already have. Due to the constraints of a published book, this single edition cannot reflect this cycling. Thus, this book is a snapshot of the Washtenaw County local food community. It does not claim to be comprehensive, nor does it claim to be the ultimate guide to the county’s local food. It is simply a curated set of tours that encourage a certain way of exploring the food community based on how it stood in late 2017 and early 2018. Another reason something/one might have been omitted was because of time constraints in the interview process. Summer is generally a busy time of year for food folks, so finding a moment to spare is rare. A “call-out” was posted in several locations around the county describing how interested and relevant parties could get in touch. Some local food operations did not meet the guidelines, which is another potential reason for omission. The main guideline was that the food operation was physically located in Washtenaw County. Further, they needed to demonstrate how they partner with a couple of other local food enterprises in the county. How many “a couple” meant was determined relative to the scale of operation; the bigger the operation, the more partners they were asked to demonstrate. We hope you enjoy the book; we enjoyed creating it. We also hope that editions emerge for other counties throughout North America.Foodloose in Washtenaw takes readers on tours to discover food-related treasures throughout a Midwestern county. From centennial farms to trendy restaurants, the self-guided tours of Foodloose offer an opportunity to explore where food is grown, produced, distributed, and enjoyed in Washtenaw County Michigan. Celebrate a vibrant, historic and expanding local food community, learn more about a unique and growing local food system, and maybe even find a new favorite place to dine.https://deepblue.lib.umich.edu/bitstream/2027.42/143841/1/Landeryou, T. and R. De Young (2018) Foodloose in Washtenaw, Michigan Publishing, University of Michigan, Ann Arbor, MI.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143841/4/9781607854661.jpghttps://deepblue.lib.umich.edu/bitstream/2027.42/143841/5/Foodloose 4_3_2018 gray.pdfDescription of Landeryou, T. and R. De Young (2018) Foodloose in Washtenaw, Michigan Publishing, University of Michigan, Ann Arbor, MI.pdf : Main articleDescription of 9781607854661.jpg : CoverDescription of Foodloose 4_3_2018 gray.pdf : Book texthttp://dx.doi.org/10.3998/mpub.999699

Long-lived crowded-litter mice exhibit lasting effects on insulin sensitivity and energy homeostasis

The action of nutrients on early postnatal growth can influence mammalian aging and longevity. Recent work has demonstrated that limiting nutrient availability in the first 3 wk of life [by increasing the number of pups in the crowded-litter (CL) model] leads to extension of mean and maximal lifespan in genetically normal mice. In this study, we aimed to characterize the impact of early-life nutrient intervention on glucose metabolism and energy homeostasis in CL mice. In our study, we used mice from litters supplemented to 12 or 15 pups and compared those to control litters limited to eight pups. At weaning and then throughout adult life, CL mice are significantly leaner and consume more oxygen relative to control mice. At 6 mo of age, CL mice had low fasting leptin concentrations, and low-dose leptin injections reduced body weight and food intake more in CL female mice than in controls. At 22 mo, CL female mice also have smaller adipocytes compared with controls. Glucose and insulin tolerance tests show an increase in insulin sensitivity in 6 mo old CL male mice, and females become more insulin sensitive later in life. Furthermore, β-cell mass was significantly reduced in the CL male mice and was associated with reduction in β-cell proliferation rate in these mice. Together, these data show that early-life nutrient intervention has a significant lifelong effect on metabolic characteristics that may contribute to the increased lifespan of CL mice

Hypothalamic growth hormone receptor (GHR) controls hepatic glucose production in nutrient-sensing leptin receptor (LepRb) expressing neurons

Objective: The GH/IGF-1 axis has important roles in growth and metabolism. GH and GH receptor (GHR) are active in the central nervous system (CNS) and are crucial in regulating several aspects of metabolism. In the hypothalamus, there is a high abundance of GH-responsive cells, but the role of GH signaling in hypothalamic neurons is unknown. Previous work has demonstrated that the Ghr gene is highly expressed in LepRb neurons. Given that leptin is a key regulator of energy balance by acting on leptin receptor (LepRb)-expressing neurons, we tested the hypothesis that LepRb neurons represent an important site for GHR signaling to control body homeostasis. Methods: To determine the importance of GHR signaling in LepRb neurons, we utilized Cre/loxP technology to ablate GHR expression in LepRb neurons (LeprEYFPΔGHR). The mice were generated by crossing the Leprcre on the cre-inducible ROSA26-EYFP mice to GHRL/L mice. Parameters of body composition and glucose homeostasis were evaluated. Results: Our results demonstrate that the sites with GHR and LepRb co-expression include ARH, DMH, and LHA neurons. Leptin action was not altered in LeprEYFPΔGHR mice; however, GH-induced pStat5-IR in LepRb neurons was significantly reduced in these mice. Serum IGF-1 and GH levels were unaltered, and we found no evidence that GHR signaling regulates food intake and body weight in LepRb neurons. In contrast, diminished GHR signaling in LepRb neurons impaired hepatic insulin sensitivity and peripheral lipid metabolism. This was paralleled with a failure to suppress expression of the gluconeogenic genes and impaired hepatic insulin signaling in LeprEYFPΔGHR mice. Conclusion: These findings suggest the existence of GHR-leptin neurocircuitry that plays an important role in the GHR-mediated regulation of glucose metabolism irrespective of feeding. Keywords: Growth hormone receptor, Hypothalamus, Leptin receptor, Glucose production, Live