Location: Children's Nutrition Research Center
2022 Annual Report
Objectives
A number of pressing nutritional issues face mankind. In the US and other developed countries strategies are needed to address the ever-increasing epidemic of obesity and related chronic diseases and in impoverished countries severe acute malnutrition directly contributes to deaths of more than a million children under the age of 5 each year globally. To address these concerns researchers will conduct the following objectives: 1) compare the effects of inulin and fructo-oligosaccharides against a maltodextrin placebo in obese children, using a double-blind randomized controlled trial, to study weight loss, fecal microbiota and their functions; 2) removed due to scientists departure; and 3) conduct a clinical trial adding black-eyed peas to diets of young children at risk for stunting. Determine efficacy in reducing stunting and analyze fecal sample to understand potential mechanisms by which the food supplement ameliorates stunting. Assess dietary compliance in a novel, quantitative manner using a urinary biomarker for black eyed peas. Currently quercetin and ferulic acid are candidates for this biomarker. Additionally, breastfeeding has enormous health benefits to both infant and mother and continued efforts to understand the biology of mammary development and lactation are important to improving both infant and maternal health. Thus we will undertake this objective to further our knowledge: 4) select inbred mouse strains with phenotypic extremes in milk production will be used to: a) identify genomic variants along with intestinal and mammary-expressed genes that differentiate low and high milk production, and b) determine the extent to which genome-driven differences in milk production and mammary gene expression are directly mediated through host-dependent differences in the intestinal and/or mammary tissue microbiome.
Approach
A multi-discipline approach will be undertaken to address these nutritional concerns. Hispanic children ages 7-18 years of age will be enrolled in the study, anthropometric measurements and blood draws will be taken and analyzed. Urine and stool samples will be collected and analysis will be performed to account for inulin and B-defensin. Researchers will also assess the pre- and post-treatment serum samples from a recently concluded study of 1-carbon metabolites. We will perform laboratory procedures to assess DNA methylation from the samples collected. Scientists will conduct a randomized, double blind, clinical controlled trial in south central Mali among healthy 6-12 month old children by adding black-eyed peas to diets of young children at risk for stunting. Scientists will analyze urinary and fecal samples to understand potential mechanisms by which the food supplement reduces stunting. And finally, researchers will use genome-wide pathway association study approaches in conjunction with bioinformatics tools to predict the functional consequences of the private alleles within the lactation phenome strains to better understand the phenotypic expression of increased lactation.
Progress Report
To review the progress made during the year, please refer to the following projects: 3092-51000-062-01S (Project #1), 3092-51000-062-03S (Project #2), and 3092-51000-062-04S (Project #3).
Accomplishments
1. Dietary sugars and bacteria in the gut both contribute to abdominal pain and obesity. Sugars in the diet can impact the types and function of gut bacteria, which in turn, can modify the hormones secreted by the human body that may play a role in the development of obesity. To further study this impact of sugar, researchers at the Children's Nutrition Research Center in Houston, Texas, administered two types of sugars (one easily absorbed and another not easily absorbed) to children with irritable bowel syndrome, a condition found commonly in children and adults that causes abdominal pain and changes in stool habits. In the children who developed abdominal pain in response to the poorly absorbed sugar, there was a greater abundance of a hormone associated with obesity. These results highlight the way diet and gut bacteria interact to cause abdominal pain. In addition, the results show that the types and abundance of certain bacteria can affect hormones and potentially contribute to the development of obesity. Based on this research, future studies may help guide the development of diets and treatments that could modify the gut bacterial population to one that does not cause pain and does not increase the likelihood of obesity.
Review Publications
Stephenson, K., Callaghan-Gillespie, M., Maleta, K., Nkhoma, M., George, M., Park, H., Lee, R., Humphries-Cuff, I., Lacombe, R., Wegner, D., Canfield, R., Brenna, J., Manary, M. 2021. Low linoleic acid foods with added DHA given to Malawian children with severe acute malnutrition improve cognition: A randomized, triple-blinded, controlled clinical trial. American Journal of Clinical Nutrition. https://doi.org/10.1093/ajcn/nqab363.
Parikh, P., Semba, R., Manary, M., Swaminathan, S., Udomkesmalee, E., Bos, R., Poh, B., Rojroongwasinkul, N., Geurts, J., Sekartini, R., Nga, T. 2021. Animal source foods, rich in essential amino acids, are important for linear growth and development of young children in low- and middle-income countries. Maternal and Child Nutrition. 18(1). Article e13264. https://doi.org/10.1111/mcn.13264.
Angood, C., Kerac, M., Black, R., Briend, A., Hanson, K., Jarrett, S., Manary, M., McGrath, M., Zagre, N., Lelijveld, N., Mayberry, A., CHNRI collaborators, Council of Research & Technical Advice on Acute Malnutrition (CORTASAM). 2021. Treatment of child wasting: Results of a child health and nutrition research initiative (CHNRI) prioritisation exercise. F1000Research. 10. Article 126. https://doi.org/10.12688/f1000research.46544.1.
Hendrixson, D.T., Smith, K., Lasowski, P., Callaghan-Gillespie, M., Weber, J., Papathakis, P., Iversen, P., Koroma, S., Manary, M.J. 2021. A novel intervention combining supplementary food and infection control measures to improve birth outcomes in undernourished pregnant women in Sierra Leone: A randomized, controlled clinical effectiveness trial. PLoS Medicine. https://doi.org/10.1371/journal.pmed.1003618.
Jilcott Pitts, S.B., Moran, N.E., Wu, Q., Harnack, L., Craft, N.E., Hanchard, N., Bell, R., Moe, S.G., Johnson, N., Obasohan, J., Carr-Manthe, P.L., Laska, M.N. 2021. Pressure-mediated reflection spectroscopy criterion validity as a biomarker of fruit and vegetable intake: A two-side cross-sectional study of four racial or ethnic groups. Journal of Nutrition. https://doi.org/10.1093/jn/nxab349.
Pontzer, H., Yamada, Y., Sagayama, H., Ainslie, P.N., Andersen, L.F., Anderson, L.J., Arab, L., Baddou, I., Bedu-Addo, K., Blaak, E.E., Blanc, S., Bonomi, A.G., Bouten, C.V., Bovet, P., Buchowski, M.S., Butte, N.F., Camps, S.G., Close, G.L., Cooper, J.A., Cooper, R., Das, S., Dugas, L.R., Ekelund, U., Entringer, S., Forrester, T., Fudge, B.W., Gories, A.H., Gurven, M., Hambly, C., El Hamdouchi, A., Hoos, M.B., Hu, S., Joonas, N., Joosen, A.M., Katzmarzyk, P., Kempen, K.P., Kimura, M., Kraus, W.E., Kushner, R.E., Lambert, E.V., Leonard, W.R., Lessan, N., Martin, C., Medin, A.C., Meijer, E.P., Morehen, J.C., Morton, J.P., Neuhouser, M.J., Nicklas, T.A., Ojiambo, R.M., Pietilainen, K.H., Pitsiladis, Y.P., Plange-Rhule, J., Plasqui, G., Prentice, R.L., Rabinovich, R.A., Racette, S.B., Raichlen, D.A., Ravussin, E., Reynolds, R.M., Roberts, S., Schuit, A.J., Sjodin, A.M., Stice, E., Urlacher, S.S., Valenti, G., Van Etten, L.M., Van Mil, E.A., Wells, J.C., Wilson, G., Wood, B.M., Yanovski, J., Yoshida, T., Zhang, X., Murphy-Alford, A.J., Loechl, C., Luke, A.H., Rood, J., Schoeller, D.A., Westerterp, K.R., Wong, W.W., Speakman, J.R. 2021. Daily energy expenditure through the human life course. Science. 373(6556):808-812. https://doi.org/10.1126/science.abe5017.
Westerterp, K.R., Yamada, Y., Sagayama, H., Ainslie, P.N., Andersen, L.F., Anderson, L.J., Arab, L., Baddou, I., Bedu-Addo, K., Blaak, E.E., Blanc, S., Bonami, A.G., Bouten, C.V., Bovet, P., Buchowski, M.S., Butte, N.F., Camps, S.G., Close, G.L., Cooper, J.A., Das, S.K., Cooper, R., Dugas, L.R., Ekelund, U., Entringer, S., Forrester, T., Fudge, B.W., Goris, A.H., Gurven, M., Hambly, C., El Hamdouchi, A., Hoos, M.B., Hu, S., Joonas, N., Joosen, A.M., Katzmarzyk, P., Kempen, K.P., Kimura, M., Kraus, W.E., Kushner, R.F., Lambert, E.V., Leonard, W.R., Lessan, N., Martin, C.K., Medin, A.C., Meijer, E.P., Morehen, J.C., Morton, J.P., Neuhauser, M.L., Nicklas, T.A., Ojiambo, R.M., Pietilainen, K.H., Pitsiladis, Y.P., Plange-Rhule, J., Plasqui, G., Prentice, R.L., Rabinovich, R.A., Racette, S.B., Raichlen, D.A., Ravussin, E., Reynolds, R.M., Roberts, S., Schuit, A.J., Sjodin, A.M., Stice, E., Urlacher, S.S., Valenti, G., Van Etten, L.M., Van Mil, E.A., Wells, J.C., Wilson, G., Wood, B.M., Yanovski, J., Yoshida, T., Zhang, X., Murphy-Alford, A.J., Loechl, C.U., Luke, A.H., Pontzer, H., Rood, J., Schoeller, D.A., Wong, W.W., Speakman, J.R. 2021. Physical activity and fat-free mass during growth and in later life. American Journal of Clinical Nutrition. https://doi.org/10.1093/ajcn/nqab260.
Zhu, Y. 2022. Gap junction-dependent and -independent functions of connexin43 in biology. Biology. 11(2):283. https://doi.org/10.3390/biology11020283.
Febo-Rodriquez, L., Chumpitazi, B.P., Sher, A.C., Shulman, R.J. 2021. Gastric accommodation: Physiology, diagnostic modalities, clinical relevance, and therapies. Neurogastroenterology & Motility. 33(12). Article e14213. https://doi.org/10.1111/nmo.14213.
Thapar, N., Benninga, M.A., Crowell, M.D., Di Lorenzo, C., Mack, I., Nurko, S., Saps, M., Shulman, R.J., Szajewska, H., Van Tilburg, M.A., Enck, P. 2020. Paediatric functional abdominal pain disorders. Nature Review Disease Primers. 6. Artticle 89. https://doi.org/10.1038/s41572-020-00222-5.
Rajabi, T., Schell, S.K., Agapova, S.E., Hassa, A., Zalta, M., Wegner, D.R., Callaghan-Gillespie, M., Koroma, A., Kamara, M.T., Manary, M.J., Stephenson, K.B. 2022. Supplementary feeding of moderately wasted children in Sierra Leone reduces severe acute malnutrition and death when compared with nutrition counseling: A retrospective cohort study. Journal of Nutrition. 152(4):1149-1158. https://doi.org/10.1093/jn/nxab451.
Sayre-Chavez, B., Baxter, B., Broeckling, C.D., Munoz-Amatriain, M., Manary, M., Ryan, E.P. 2022. Non-targeted metabolomics of cooked cowpea (Vigna unguiculate) and pigeon pea (Cajanus cajan) from Ghana using two distinct and complementary platforms. Food Chemistry: Molecular Sciences. 4. Article 100087. https://doi.org/10.1016/j.fochms.2022.100087.
Shulman, R.J., Chumpitazi, B.P., Abdel-Rahman, S.M., Garg, U., Musaad, S., Kearns, G.L. 2021. Randomised trial: Peppermint oil (menthol) pharmacokinetics in children and effects on gut motility in children with functional abdominal pain. British Journal Of Clinical Pharmacology. 88:1321-1333. https://doi.org/10.1111/bcp.15076.
Zhu, Y., Li, N., Huang, M., Bartels, M., Dogne, S., Zhao, S., Chen, X., Crewe, C., Straub, L., Vishvanath, L., Zhang, Z., Shao, M., Yang, Y., Gliniak, C.M., Gordillo, R., Smith, G.I., Holland, W.L., Gupta, R.K., Dong, B., Caron, N., Xu, Y., Akgul, Y., Klein, S., Scherer, P.E. 2021. Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis. Nature Communications. 12. Article 4829. https://doi.org/10.1038/s41467-021-25025-4.
Koch, K.L., Van Natta, M., Parkman, H.P., Grover, M., Abell, T.L., McCallum, R.W., Shaltout, H.A., Sarosiek, I., Farrugia, G., Shulman, R.J., Tonascia, J., Miriel, L., Hamilton, F., Pasricha, P.J. 2022. Effect of liquid and solid test meals on symptoms and gastric myoelectrical activity in patients with gastroparesis and functional dyspepsia. Neurogastroenterology & Motility. https://doi.org/10.1111/nmo.14376.
Kaul, I., Staggs, V.S., Bagherian, A., Ali, A., Shulman, R.J., Colombo, J.M., Schurman, J.V., Chumpitazi, B.P., Friesen, C.A. 2022. Pediatric Rome IV diagnosis agreement is greater than agreement on diagnostic testing. Neurogastroenterology & Motility. https://doi.org/10.1111/nmo.14355.
Hollier, J.M., Salemi, J.L., Shulman, R.J. 2021. United States healthcare burden of pediatric functional gastrointestinal pain disorder hospitalizations from 2002 to 2018. Neurogastroenterology & Motility. 34(7). Article e14288. https://doi.org/10.1111/nmo.14288.
Kellermayer, R., Wu, Q., Nagy-Szakal, D., Queliza, K., Ihekweazu, F.D., Bocchini, C.E., Magee, A.R., Oezguen, N., Spinler, J.K., Hollister, E.B., Shulman, R.J., Versalovic, J., Luna, R., Savidge, T.C. 2022. Fecal microbiota transplantation commonly failed in children with co-morbidities. Journal of Pediatric Gastroenterology and Nutrition. 74(2):227-235. https://doi.org/10.1097/MPG.0000000000003336.
Thapa, S., Luna, R., Chumpitazi, B.P., Oezguen, N., Abdel-Rahman, S.M., Garg, U., Musaad, S., Versalovic, J., Kearns, G.L., Shulman, R.J. 2022. Peppermint oil effects on the gut microbiome in children with functional abdominal pain. Clinical and Translational science. 15:1036-1049. https://doi.org/10.1111/cts.13224.
Parkman, H.P., Van Natta, M.L., Maurer, A.H., Koch, K.L., Grover, M., Malik, Z., Sarosiek, I., Abell, T.L., Bulat, R., Kuo, B., Shulman, R.J., Farrugia, G., Miriel, L., Tonascia, J., Hamilton, F., Pasricha, P.J., McCallum, R.W. 2022. Postprandial symptoms in patients with symptoms of gastroparesis roles of gastric emptying and accommodation. American Journal of Physiology - Gastrointestinal and Liver Physiology. 323:G44-G59. https://doi.org/10.1152/ajpgi.00278.2021.
Narayana, V., McMeans, A.R., Levy, R.L., Shulman, R.J., Chumpitazi, B.P. 2022. Children with functional abdominal pain disorders successfully decrease FODMAP food intake on a low FODMAP diet with modest improvements in nutritional intake and diet quality. Neurogastroenterology & Motility. https://doi.org/10.1111/nmo.14392.
Parkman, H.P., Van Natta, M.L., Makol, A., Grover, M., Mccallum, R.W., Malik, Z., Koch, K.L., Sarosiek, I., Kuo, B., Shulman, R.J., Farrugia, G., Miriel, L., Tonascia, J., Hamilton, F., Pasricha, P.J., Abell, T.L. 2021. Prevalence and clinical correlates of antinuclear antibody in patients with gastroparesis. Neurogastroenterology & Motility. 34(5):e14270. https://doi.org/10.1111/nmo.14270.
Febo-Rodriguez, L., Chumpitazi, B.P., Musaad, S., Sher, A.C., Varni, J.W., Shulman, R.J. 2022. Gastrointestinal symptoms profile in pediatric patients with gastroparesis compared to healthy controls. Journal of Pediatric Gastroenterology and Nutrition. https://doi.org/10.1097/MPG.0000000000003484.
Sarosiek, I., Van Natta, M., Parkman, H.P., Abell, T., Koch, K.L., Kuo, B., Shulman, R.J., Farrugia, G., Grover, M., Hamilton, F.A., Pasricha, P.J., Yates, K.P., Miriel, L., Wilson, L., Yamada, G., Tonascia, J., Mccallum, R.W. 2021. Effect of domperidone therapy on gastroparesis symptoms results of a dynamic cohort study by NIDDK Gastroparesis Consortium. Clinical Gastroenterology and Hepatology. 20:e452-e464. https://doi.org/10.1016/j.cgh.2021.05.063.
Varni, J.W., Shulman, R.J., Self, M.M., Febo-Rodriguez, L., Charron, H., Williams, K., Nurko, S., Rosen, R.L., Chumpitazi, B.P. 2021. PedsQL(TM) gastroparesis symptoms module domain and item development: Qualitative methods. Journal of Pediatric Gastroenterology and Nutrition. 73(2):192-196. https://doi.org/10.1097/MPG.0000000000003146.
Boonma, P., Shapiro, J.M., Hollister, E.B., Badu, S., Wu, Q., Weidler, E.M., Abraham, B.P., Devaraj, S., Luna, R., Versalovic, J., Heitkemper, M.M., Savidge, T.C., Shulman, R.J. 2021. Probiotic VSL#3 treatment reduces colonic permeability and abdominal pain symptoms in patients with irritable bowel syndrome. Frontiers in Pain Research. 2. Article 691689. https://doi.org/10.3389/fpain.2021.691689.
Leppanen, J.M., Butcher, J.W., Godbout, C., Stephenson, K., Hendrixson, D., Griswold, S., Rogers, B.L., Webb, P., Koroma, A.S., Manary, M.J. 2022. Assessing infant cognition in field settings using eye-tracking: A pilot cohort trial in Sierra Leone. BMJ Open. 12. Article e049783. https://doi.org/10.1136/bmjopen-2021-049783.
Singh, A., Potani, I., Griswold, S.P., Suri, D., Langlois, B., Shen, Y., Walton, S.M., Kwan Ho Chui, K., Manary, M.J., Webb, P., Rogers, B.L., Rosenberg, I.H. 2021. Host fecal mRNAs predicted environmental enteric dysfunction among children with moderate acute malnutrition in Sierra Leone. American Journal of Tropical Medicine and Hygiene. 105(5):1376-1382. https://doi.org/10.4269/ajtmh.21-0348.
May, T., De La Haye, B., Nord, G., Klatt, K., Stephenson, K., Adams, S., Bollinger, L., Hanchard, N., Arning, E., Bottiglieri, T., Maleta, K., Manary, M., Jahoor, F. 2022. One-carbon metabolism in children with marasmus and kwashiorkor. EBioMedicine. 75. Article 103791. https://doi.org/10.1016/j.ebiom.2021.103791.
Tu, L., Zhang, N., Conde, K., Bean, J., Wang, C., Xu, Y. 2021. Free-floating immunostaining of mouse brains. The Journal of Visualized Experiments (JoVE). 176. Article e62876. https://doi.org/10.3791/62876.
Yang, Y., He, Y., Liu, H., Zhou, W., Wang, C., Xu, P., Cai, X., Liu, H., Yu, K., Pei, Z., Hyseni, I., Fukuda, M., Tong, Q., Xu, J., Sun, Z., O'Malley, B., Xu, Y. 2021. Hypothalamic steroid receptor coactivator-2 regulates adaptations to fasting and overnutrition. Cell Reports. 37. Article 110075. https://doi.org/10.1016/j.celrep.2021.110075.
He, Y., Cai, X., Liu, H., Conde, K., Xu, P., Li, Y., Wang, C., Yu, M., He, Y., Liu, H., Liang, C., Yang, T., Yang, Y., Yu, K., Wang, J., Zheng, R., Liu, F., Sun, Z., Heisler, L., Wu, Q., Tong, Q., Zhu, C., Shu, G., Xu, Y. 2021. 5-HT recruits distinct neurocircuits to inhibit hunger-driven and non-hunger-driven feeding. Molecular Psychiatry. 26:7211-7224. https://doi.org/10.1038/s41380-021-01220-z.
Zhang, N., Yan, Z., Liu, H., Yu, M., He, Y., Liu, H., Liang, C., Tu, L., Wang, L., Yin, N., Han, J., Scarcelli, N., Yang, Y., Wang, C., Zeng, T., Chen, L., Xu, Y. 2021. Hypothalamic perineuronal nets are regulated by sex and dietary interventions. Frontiers in Physiology. 12. Article 714104. https://doi.org/10.3389/fphys.2021.714104.
Liu, H., Wang, C., Yu, M., Yang, Y., He, Y., Liu, H., Liang, C., Tu, L., Zhang, N., Wang, L., Wang, J., Liu, F., Hu, F., Xu, Y. 2021. TPH2 in the dorsal raphe nuclei regulates energy balance in a sex-dependent manner. Endocrinology. 162(1):1-16. https://doi.org/10.1210/endocr/bqaa183.
Wang, C., Zhou, W., He, Y., Yang, T., Xu, P., Yang, Y., Cai, X., Wang, J., Liu, H., Yu, M., Liang, C., Yang, T., Liu, H., Fukuda, M., Tong, Q., Wu, Q., Sun, Z., He, Y., Xu, Y. 2021. AgRP neurons trigger long-term potentiation and facilitate food seeking. Translational Psychiatry. 11. Article 11. https://doi.org/10.1038/s41398-020-01161-1.
Yu, K., He, Y., Hyseni, L., Pei, Z., Yang, Y., Xu, P., Cai, X., Liu, H., He, Y., Yu, M., Liang, C., Yang, T., Wang, J., Gourdy, P., Arnal, J., Lenfant, F., Xu, Y., Wang, C. 2020. 17B-estradiol promotes acute refeeding in hungry mice via membrane-initiated ERa signaling. Molecular Metabolism. 42. Article 101053. https://doi.org/10.1016/j.molmet.2020.101053.
Hendrixson, T., Manary, M.J., Trehan, I., Wall, L.L. 2021. Undernutrition in pregnancy: Evaluation, management, and outcome in resource-limited areas. UpToDate. Available at: https://www.uptodate.com/contents/undernutrition-in-pregnancy-evaluation-management-and-outcome-in-resource-limited-areas
Trehan, I., Manary, M.J. 2022. Management of moderate acute malnutrition in children in resource-limited countries. In UpToDate. Available at: https://www.uptodate.com/contents/management-of-moderate-acute-malnutrition-in-children-in-resource-limited-countries
Trehan, I., Manary, M.J. 2021. Management of uncomplicated severe acute malnutrition in children in resource-limited countries. UpToDate. Available at: https://www.uptodate.com/contents/management-of-uncomplicated-severe-acute-malnutrition-in-children-in-resource-limited-countries
Trehan, I., Manary, M.J. 2021. Management of complicated severe acute malnutrition in children in resource-limited countries. UpToDate. Available at: https://www.uptodate.com/contents/management-of-complicated-severe-acute-malnutrition-in-children-in-resource-limited-countries
Ye, H., Feng, B., Wang, C., Saito, K., Yang, Y., Obrahimi, L., Schaul, S., Patel, N., Saenz, L., Luo, P., Lai, P., Torres, V., Kota, M., Dixit, D., Cai, X., Qu, N., Hyseni, I., Yu, K., Jiang, Y., Tong, Q., Sun, Z., Arenkiel, B.R., He, Y., Xu, P., Xu, Y. 2022. An estrogen-sensitive hypothalamus-midbrain neural circuit controls thermogenesis and physical activity. Science Advances. 8(3). Article eabk0185. https://doi.org/10.1126/sciadv.abk0185.
Huang, M., Song, A., Chen, X., Ishtiaq, S., Wang, C., Hadsell, D.L., Wang, Q.A., Zhu, Y. 2022. Maternal adipocyte connexin43 gap junctions affect breastmilk lactose levels and neonate growth in mice. Biology. 11(7). Article 1023. https://doi.org/10.3390/biology11071023.
Pasricha, P.J., Grover, M., Yates, K.P., Abell, T.L., Koch, K.L., Mccallum, R.W., Sarosiek, I., Bernard, C.E., Kuo, B., Bulat, R., Shulman, R., Chumpitazi, B.P., Tonascia, J., Miriel, L.A., Wilson, L.A., Van Natta, M.L., Mitchell, E., Hamilton, F., Farrugia, G., Parkman, H.P. 2022. Progress in gastroparesis - A narrative review of the work of the gastroparesis clinical research consortium. Clinical Gastroenterology and Hepatology. 20(12):2684-2695.e3. https://doi.org/10.1016/j.cgh.2022.05.022.
Zhu, Y., Li, N., Huang, M., Chen, X., An, Y.A., Li, J., Zhao, S., Funcke, J., Cao, J., He, Z., Zhu, Q., Zhang, Z., Wang, Z.V., Xu, L., Williams, K.W., Li, C., Grove, K., Scherer, P.E. 2022. Activating connexin43 gap junctions primes adipose tissue for therapeutic intervention. Acta Pharmaceutica Sinica B. 12(7):3063-3072. https://doi.org/10.1016/j.apsb.2022.02.020.