Nutrition in the Prevention and Treatment of Abdominal Obesity

504 Pages·2014·26.31 MB·English

by  Ronald Ross Watson (Eds.)

NUTRITION IN THE PREVENTION AND
TREATMENT OF ABDOMINAL OBESITY
NUTRITION IN THE
PREVENTION AND
TREATMENT OF
ABDOMINAL OBESITY
Edited by
Ronald Ross Watson, Bs, PhD
University of Arizona, Division of Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health,
and School of Medicine, Arizona Health Sciences Center, Tucson, AZ, USA
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Preface
Abdominal or visceral fat comprises fat deposits DIET, SUPPLEMENTS, AND FOODS IN
between the liver and kidneys that are packed into the THE MANAGEMENT OF VISCERAL
abdominal cavity. This fat is distinct from subcutaneous OBESITY
and intramuscular fat because it is primarily visceral and
includes several adipose depots. Historically, such fat Understanding abdominal obesity will promote its
has a played a key role in survival in times of famine. As modification and prevention, thus reducing chronic dis-
described in the book, such fat is subject to lifestyle man- ease levels. Under standard conditions, adipose depots
agement as well as to accumulation. provide feedback on hunger and dietary needs to the
central nervous system. A variety of biochemical, physi-
ological, and food-regulated mechanisms that alter
EPIDEMIOLOGY AND CLINICAL
abdominal obesity and thus disease risk are reviewed.
MANAGEMENT OF ABDOMINAL
Maeda identifies glucagon-like peptide 1 as an agonist of
OBESITY
visceral fat adiposity and appetite. Castonguay defines
the role of fructose in hypertriglyceridemia and obesity.
Appetite-regulating gut hormones, work, diet, and
Dietary foods play key roles in visceral fat accumulation
physical activity in adults, children, and adolescents
and its removal. The effects of intermittent fasting ver-
have all been described as factors that affect abdominal
sus daily calorie restriction on visceral fat loss are com-
fat accumulation. Tarantino describes the efficacy of
pared by Trepanowski and Varady. Laurant and
physical activity in treating nonalcoholic fatty liver dis-
colleagues show that gender and exercise, which both
ease. Its actions in specific populations, for example the
modulate cytokines, affect obesity and thus heart dis-
elevated hypertension of African-Americans, are defined
ease. Stress-induced eating also affects obesity, and
and explained by Hornbuckle. Von Gruenigen shows
Finch and Tomiyama describe relevant physiological
how fat plays a role in cancer survivorship, while
and behavioral stress responses. Campbell and cowork-
Clement reviews massive obesity and its consequences.
ers review fructose-induced hypertriglyceridemia as a
Clearly, and historically, lifestyle factors are major fac-
cause of abdominal obesity that can be modified by
tors that affect abdominal fat; these are defined by Suliga
changes in food intake. Yoshinaga describes how the
with Gomez-Martinez in their review of the role of phys-
gender and lifestyle of individuals and their parents
ical activity in abdominal obesity in adolescents.
combine to modify obesity.
Therapies including surgery and sleeve gastrostomy are
Adipose tissues play important roles in health; their
reviewed by Ruiz-Tovar, while the beneficial effects of
primary role is as a reserve of lipids needed to provide
supplemental magnesium are defined by Kokot.
energy. Fat tissues consist of about 86% fat, and a variety
Fat is constantly being stored and released from adi-
of different cell types regulate fat accumulation. Lipolysis
pose tissue. Storage in adipose tissue is regulated by is modulated by lipolytic β-adrenergic receptors and
insulin and stimulated by high serum glucose. Thus, fat antilipolysis is regulated by α2A adrenergic receptors.
cells have an important role in maintaining triglyceride
Dietary foods and supplements can play critical roles in
and free fatty acid levels. However, abdominal fat is
modifying and preventing such fat accumulation. Park
more prone to inducing insulin resistance; therefore,
describes several types of soy protein and fermented
central obesity is a marker of impaired glucose tolerance
soypastes that can reduce visceral obesity. Reviews by
as a risk factor for many obesity-related diseases. Gasevic
the Pimentel and Bautista-Castaño groups describe
et al. show that adipose tissue affects insulin resistance
the roles of alcohol, coffee, and bread in modifying
and is further modified by ethnicity. In addition, Rossi
obesity through various mechanisms, including immu-
and colleagues describe visceral fat as key to ectopic fat
nomodulation of inflammation, which is obesity
accumulation, while Leblanc and Poirier discuss how
induced. As Nagai and Takatsu review in humans and
high blood pressure risk is lessened by reducing visceral
Masternak in animal models, these mechanisms are
obesity. Finally, Prasad defines the problems of advanced
important in metabolic disorders associated with chronic
glycation end-products in relation to adiposity.
diseases. Castonguay and coauthors describe appetite
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xiv
Preface
and reward signals in the brain, with sugar being a major describes the effects of dietary fatty acids on weight, fat
mediator, as shown by magnetic resonance imaging. mass and abdominal fat. Park shows that conjugated lin-
Additionally, the effects of dietary supplements on fat oleic acid benefits human health by controlling weight.
regulation and thus visceral obesity are an important Finally, D’Antona reviews the current evidence that
focus of this book. A stringent vegan diet with dietary amino acid supplementation affects obesity. Free fatty
restriction produces significant weight loss. A supplement acids are released from lipoproteins by enzymes and
containing flaxseed components changes visceral o besity, enter adipocytes to be reassembled into triglycerides for
inflammation, lipids, and chronic hypertension, as Park storage. Through regulating adipose tissues in visceral
summarizes. Damms-Machado shows that nutritional fat, different cell types (primarily adipocytes, fibroblasts,
deficiencies in obese patients are a common condition, macrophages, lymphocytes, and endothelial cells) can
which are additionally impacted by bariatric operations, have wide-ranging effects on health. Matikainen
like sleeve gastrectomy. Miyashita and Hosokawa show describes the role of fibroblast growth factor 21 in regu-
the importance of plant carotenoids as nutraceutical lating energy metabolism in adipose tissues to promote
therapies for visceral obesity. health. Qi discusses how polymorphisms in the gene
Other macromolecules and foods are modulators of encoding neuropeptide Y (and other genes) affect central
visceral fat and play a key role in a host of diseases, obesity. Finally, Garaulet defines site-specific adipose tis-
including diabetes, insulin resistance, cardiovascular sue fatty acid composition and its role in the regulation
disease, inflammation, and other obesity-related health of abdominal obesity.
problems. Pal and coauthors describe a role for psyllium In conclusion, the authors describe how factors that
as a therapy for obesity comorbidities. Karl and McKeown affect the current abdominal obesity epidemic will pro-
describe the role of whole grain (with its intrinsic fiber) vide major benefits by preventing chronic diseases, espe-
in obesity prevention, while Pal defines a similar role for cially heart, vascular, and diabetic diseases. A broad
dietary whey protein. Vajro and coworkers describe the range of disciplines are involved in dealing with the con-
role of other complex carbohydrates known as probiotics sequences of excessive abdominal fat, including cardiol-
in treating hepatic obesity and related diseases. Dinner ogy, diabetes research, endocrinology, exercise
carbohydrates, if used as described by Madar and col- physiology, and studies focusing on lipids, metabolism,
leagues, produce weight loss and have other effects on nutrition, and obesity. We describe how abdominal obe-
visceral fat. Citrus is a food that, as Mukai describes in sity, a major cause of mortality and morbidity in much of
animal models and humans, changes visceral fat accu- the world through its associated diseases, can be regu-
mulation. Lipids are the major modulators of fat. Tan lated by food and dietary therapies.
Acknowledgments
The work of Dr. Watson’s editorial assistant, Bethany research into natural health and wellness. It is commit-
L. Stevens, and the project managers, Megan Wickline ted to promoting scientific evidence for the usefulness
and Jeffrey Rossetti, in communicating with authors and and cost-effectiveness of diet, supplements, and a
working on the manuscripts was critical to the success- healthy lifestyle in improving health and wellness, and
ful completion of the book. It is very much appreciated. reducing disease. Finally, the work of Mari Stoddard,
Support for the work of Ms. Stevens and Dr. Watson was the librarian of the Arizona Health Science Library, was
graciously provided by the Natural Health Research vital and very helpful in identifying key researchers who
Institute (www.naturalhealthresearch.org), an indepen- participated in the book.
dent, nonprofit organization that supports science-based
xv
Contributors
Machiko Aoki, MD, PhD Department of Pediatrics, Aoki Magdy El-Salhy, MD, PhD Section for Gastroenterology,
Clinic of Internal Medicine, Cardiovascular Medicine & Department of Medicine, Stord Helse-Fonna Hospital,
Pediatrics, Fukuoka, Japan. Norway.
Inmaculada Bautista-Castaño, MD, PhD Department of Section for Gastroenterology, Department of Clinical Medicine,
Clinical Sciences, University of Las Palmas de Gran Canaria, University of Bergen, Norway.
Las Palmas de Gran Canaria, Spain Biomedical Research Francesco Fantin, MD, PhD Division of Geriatric
Center Network on Obesity and Nutrition (CIBERobn) Medicine, University of Verona, Ospedale Maggiore,
Physiopathology of Obesity and Nutrition, Institute of Verona, Italy.
Health Carlos III, Madrid, Spain. Laura E. Finch, B.S. Cornell University Department of
Paolo Bertassello, MD Division of Geriatric Medicine, Psychology, Los Angeles, CA, USA.
University of Verona, Ospedale Maggiore, Verona, Italy. Carmine Finelli, MD, PhD INT “Fondazione Pascale” -
Stephan C. Bischoff, MD, Prof. Institute of Nutritional Cancer Research Center of Mercogliano, Mercogliano (AV),
Medicine, University of Hohenheim, Stuttgart, Germany. Italy.
Rafael Calpena, MD, PhD Department of Surgery, Bariatric Gershon Fink, MD Kaplan Medical Center, Rehovot, Israel.
Surgery Unit, General University Hospital Elche, Alicante, Yuya Fujishima, MD Department of Metabolic Medicine,
Spain. Graduate School of Medicine, Osaka University, Osaka,
Eric Campbell Department of Nutrition and Food Science, Japan.
University of Maryland, College Park, MD, USA. Marta Garaulet, PhD, Full Professor of Physi ology,
Department of Physiology, Faculty of Biology, University of
Raquel Canuto, PhD Department of Nutrition, University of
Murcia, Murcia, Spain.
Vale do Rios dos Sinos, RS, Brazil.
Danijela Gasevic, MD Department of Biomedical
Department of Nutrition, University of Caxias do Sul, RS,
Physiology and Kinesiology, Simon Fraser University,
Brazil.
Burnaby, British Columbia, Canada.
Thomas W. Castonguay, PhD Department of Nutrition and
Eliana Geller Department of Nutrition and Food Science,
Food Science, University of Maryland, College Park, MD,
University of Maryland, College Park, MD, USA.
USA.
Sonia Gómez-Martínez, PhD, Research officer Department
Karine Clément, MD, PhD Institute of Cardiometabolism
of Metabolism and Nutrition, Institute of Food Science,
and Nutrition, ICAN, Pitié-Salpêtrière Hospital; Assistance
Technology and Nutrition, Spanish National Research
Publique-Hôpitaux de Paris, CRNH-Ile de France, Paris,
Council, Madrid, Spain.
France.
Doris Gundersen, PhD Department of Research, Helse-
Anderson da Silva Garcez, MD Postgraduate Program in
Fonna, Haugesund, Norway.
Collective Health, University of Vale do Rios dos Sinos, RS,
Martin Hagger School of Public Health; Curtin Health
Brazil.
Innovation Research Institute; Curtin University of
Antje Damms-Machado, PhD Institute of Nutritional
Technology, Perth, Western Australia, Australia.
Medicine, University of Hohenheim, Stuttgart, Germany.
Takashi Hamajima, MD Department of Endocrinology and
Roberta D’Aniello, MD Department of Medicine and Metabolism, Aichi Children’s Health and Medical Center,
Surgery, Medical School of Salerno, Baronissi, Salerno, Italy. Motiokamachi, Obu, Aichi, Japan.
Giuseppe D’Antona, MD, PhD Department of Molecular Jan Gunnar Hatlebakk, MD, PhD Section for
Medicine and the Laboratory for the Study of Motor Gastroenterology, Institute of Medicine, University of
Activities in Rare Diseases, University of Pavia, Voghera, Bergen, Norway.
Italy.
Trygve Hausken, MD, PhD Section for Gastroenterology,
Sylwia Dzięgielewska-Gęsiak Department of Internal Department of Clinical Medicine, University of Bergen,
Diseases, Silesian Medical University, Katowice, Poland. Norway.
xvii
xviii
Contributors
Section for Gastroenterology, Department of Medicine, Faculty of Teacher Training and Education, Universidad
Haukland University Hospital, Bergen, Norway. Autónoma de Madrid, Madrid, Spain.
Suleen Ho, PhD, Hons School of Public Health, Curtin Grazia Massa, RD Department of Medicine and Surgery,
Health Innovation Research Institute, Curtin University of Medical School of Salerno, Baronissi, Salerno, Italy.
Technology, Perth, Western Australia, Australia. Michal M. Masternak, PhD University of Central Florida,
Lyndsey M. Hornbuckle, PhD, RD Department of Exercise Burnett School of Biomedical Sciences, College of Medicine,
Science and Sport Management, Kennesaw State University, Orlando, FL, USA.
Kennesaw, Georgia, USA. Niina Matikainen, MD, PhD Department of Endocrinology
Masashi Hosokawa Faculty of Fisheries Sciences, Hokkaido and Cardiovascular Research Unit, Heart and Lung Center,
University, Hakodate, Japan. Helsinki University Central Hospital, University of
Helsinki, Helsinki, Finland.
Samantha M. Hudgins Department of Nutrition and Food
Science, University of Maryland, College Park, MD, USA. Michele L. McCarroll, PhD Department of Obstetrics and
Gynecology, Summa Health System, Akron, Ohio, USA.
Gary R. Hunter, PhD Department of Human Studies,
University of Alabama at Birmingham, Birmingham, Jenny-Lee McKay, BSc School of Public Health, Curtin
Alabama, USA. Health Innovation Research Institute, Curtin University of
Technology, Perth, Western Australia, Australia.
Monica Jane, BSc School of Public Health, Curtin Health
Innovation Research Institute, Curtin University of Nicola M. McKeown, PhD Jean Mayer USDA Human
Technology, Perth, Western Australia, Australia. Nutrition Research Center on Aging, Tufts University,
Boson, MA, USA.
J. Philip Karl, MS, RD Jean Mayer USDA Human Nutrition
Research Center on Aging, Tufts University, Boson, MA, Thayana O. Micheletti Department of Internal Medicine,
USA. Faculty of Medical Sciences, University of Campinas
(UNICAMP), São Paulo, Brazil.
Nadia Khan MD, MSc Department of Medicine, University
of British Columbia, Vancouver, British Columbia, Canada. Kazuo Miyashita Faculty of Fisheries Sciences, Hokkaido
Simi Kohli, MD, MSc Department of Biomedical Physiology University, Hakodate, Japan.
and Kinesiology, Simon Fraser University, Burnaby, British Ayumi Miyazaki, MD, PhD Department of Pediatrics, Japan
Columbia, Canada. Community Health Care Organization Takaoka-Fushiki
Teresa Kokot, MD, PhD Department of Internal Diseases, Hospital, Takaoka, Toyama, Japan.
Silesian Medical University, Katowice, Poland. Małgorzata Muc-Wierzgoń Department of Internal Diseases,
Pascal Laurant, PhD Laboratoire Pharm-Ecologie Cardio- Silesian Medical University, Katowice, Poland.
vasculaire, UFRip Sciences Technologies Santé, Université Katsuyuki Mukai R&D Center, UNITIKA Ltd, Uji, Kyoto,
d’Avignon et des Pays du Vaucluse, Avignon, France. Japan.
Scott A. Lear, PhD Faculty of Health Sciences, Simon Fraser Yoshinori Nagai, MD, PhD, FAHA Department of Immuno-
University, Vancouver, British Columbia, Canada. biology and Pharmacological Genetics, Graduate School of
Marie-Ève Leblanc, RN, MSc Faculty of Pharmacy, Medicine and Pharmaceutical Science for Research,
University of Toyama, Toyama-shi, Toyama, Japan.
Université Laval and Institut Universitaire de Cardiologie
et de Pneumologie de Québec, Quebec City, Quebec, Masami Nagashima, MD, PhD, FAHA Department of
Canada. Rehabilitation, Aichi Saiseikai Rehabilitation Hospital,
Myoungsook Lee, PhD Department of Food and Nutrition, Nishi-ku, Nagoya, Japan.
and Research Institute of Obesity Sciences, Sungshin Astrid Nehlig French Medical Research Institute, INSERM
Women’s University, Seoul, Korea. U 663, Faculty of Medicine, Strasbourg, France.
Zecharia Madar Kaplan Medical Center, Rehovot, Israel. Ewa Nowakowska-Zajdel Department of Internal Diseases,
Norikazu Maeda, MD, PhD Department of Metabolic Silesian Medical University, Katowice, Poland.
Medicine, Graduate School of Medicine, Osaka University, Maria Teresa Anselmo Olinto, PhD Postgraduate Program
Osaka, Japan. in Collective Health, University of Vale do Rios dos Sinos,
Ascensión Marcos Department of Metabolism and RS, Brazil.
Nutrition, Institute of Food Science, Technology and Department of Nutrition, Federal University of Health Science
Nutrition, Spanish National Research Council, Madrid, of Porto Alegre, RS, Brazil.
Spain. Sebely Pal, PhD, Hons School of Public Health, Curtin
David Martínez-Gómez, PhD, Associate lecturer Depart- Health Innovation Research Institute, Curtin University of
ment of Physical Education, Sports and Human Movement, Technology, Perth, Western Australia, Australia.
xix
Contributors
Giulia Paolella, MD Department of Medicine and Surgery, Almudena Sanchez-Villegas DPharm, PhD Department of
Medical School of Salerno, Baronissi, Salerno, Italy. Clinical Sciences, University of Las Palmas de Gran Canaria,
Jae B. Park Diet, Genomics, and Immunology Laboratory, Las Palmas de Gran Canaria, Spain Biomedical Research
Beltsville Human Nutrition Research Center, United States Center Network on Obesity and Nutrition (CIBERobn)
Department of Agriculture Agricultural Research Service, Physiopathology of Obesity and Nutrition, Institute of
Beltsville, MD, USA. Health Carlos III, Madrid, Spain.
Yeonhwa Park Department of Food Science, University of Maria Sangermano, MD Department of Medicine and
Massachusetts, Amherst, MA, USA. Surgery, Medical School of Salerno, Baronissi, Salerno, Italy.
Yongsoon Park, PhD Department of Food and Nutrition, E. Sartori, MD Division of Geriatric Medicine, University of
Hanyang University, Seoul, Korea. Verona, Ospedale Maggiore, Verona, Italy.
Zdenka Pausova, MD The Hospital for Sick Children, Anna Schlappal, PhD Department of Nutrition and Food
University of Toronto, Toronto, Canada. Science, University of Maryland, College Park, MD, USA.
Fátima Pérez de Heredia, PhD Lecturer in Physiology, Luis Serra-Majem MD, PhD Department of Clinical Sciences,
School of Natural Sciences and Psychology, Liverpool John University of Las Palmas de Gran Canaria, Las Palmas de
Moores University, Liverpool, United Kingdom. Gran Canaria, Spain Biomedical Research Center Network
on Obesity and Nutrition (CIBERobn) Physiopathology of
Luca Pierri, MS Department of Medicine and Surgery,
Obesity and Nutrition, Institute of Health Carlos III, Madrid,
Medical School of Salerno, Baronissi, Salerno, Italy.
Spain.
Gustavo D. Pimentel Department of Internal Medicine,
Masaki Shinomiya, MD, PhD Department of Internal
Faculty of Medical Sciences, University of Campinas
Medicine, Nishifuna Naika, Funabashi, Chiba, Japan.
(UNICAMP), São Paulo, Brazil.
Sigal Sofer, MSc, RD Institute of Biochemistry, Food Science
Cristina Pizza, MS Department of Medicine and Surgery,
and Nutrition, The Robert H. Smith Faculty of Agriculture,
Medical School of Salerno, Baronissi, Salerno, Italy.
Food and Environment, The Hebrew University of Jerusalem,
Marco Poeta, MS Department of Medicine and Surgery,
Jerusalem, Israel.
Medical School of Salerno, Baronissi, Salerno, Italy.
Aliza Stark, PhD, RD Institute of Biochemistry, Food Science
Paul Poirier, MD, PhD, FRCPC, FACC, FAHA Faculty of
and Nutrition, The Robert H. Smith Faculty of Agriculture,
Pharmacy, Université Laval and Institut Universitaire de
Food and Environment, The Hebrew University of Jerusalem,
Cardiologie et de Pneumologie de Québec, Quebec City,
Jerusalem, Israel.
Quebec, Canada.
Edyta Suliga, PhD Department of the Prevention of
Christine Poitou, MD, PhD Institute of Cardiometabolism
Alimentary Tract Diseases, Faculty of Health Sciences, Jan
and Nutrition, ICAN, Pitié-Salpêtrière Hospital; Assistance
Kochanowski University, Kielce, Poland.
Publique-Hôpitaux de Paris, CRNH-Ile de France, Paris,
Kiyoshi Takatsu, PhD Toyama Prefectural Institute for
France.
Pharmaceutical Research, Imizu City, Toyama, Japan.
Lu Qi, MD, PhD Department of Nutrition, Harvard School of
Katsuhiko Takayanagi R&D Center, UNITIKA Ltd, Uji,
Public Health, Boston, MA, USA.
Kyoto, Japan.
Channing Division of Network Medicine, Department of
Sze Yen Tan, PhD, APD University of South Australia, School
Medicine, Brigham and Women’s Hospital and Harvard
of Pharmacy and Medical Sciences, Adelaide, Australia.
Medical School, Boston, MA, USA.
Giovanni Tarantino, MD Department of Clinical Medicine
Simone Radavelli-Bagatini, PhD, Hons School of Public
and Surgery, Federico II University Medical School of
Health, Curtin Health Innovation Research Institute, Curtin
Naples, Naples, Italy and INT “Fondazione Pascale” - Cancer
University of Technology, Perth, Western Australia,
Research Center of Mercogliano, Mercogliano (AV), Italy.
Australia.
A. Janet Tomiyama, PhD Department of Psychology,
Catherine Riva, PhD Laboratoire Pharm-Ecologie Cardiovas-
University of California, Los Angeles, CA, USA.
culaire, UFRip Sciences Technologies Santé, Université
d’Avignon et des Pays du Vaucluse, Avignon, France. John F. Trepanowski, MS Department of Kinesiology and
Nutrition, University of Illinois, Chicago, Chicago, IL, USA.
Andrea P. Rossi, MD, PhD Division of Geriatric Medicine,
University of Verona, Ospedale Maggiore, Verona, Italy. Pietro Vajro, MD Department of Medicine and Surgery,
Medical School of Salerno, Baronissi, Salerno, Italy.
G. Dante Roulette, MD Department of Obstetrics and
Gynecology, Summa Health System, Akron, Ohio, USA. European Laboratory for the Investigation of Food-Induced
Diseases, University of Naples Federico II, Naples, Italy.
Jaime Ruiz-Tovar, MD, PhD Department of Surgery,
Bariatric Surgery Unit, General University Hospital Elche, Krista Varady, PhD Department of Kinesiology and
Alicante, Spain. Nutrition, University of Illinois, Chicago, Chicago, IL, USA.
xx
Contributors
Camille Vatier, MD Institute of Cardiometabolism and Shanghai Clinical Center for Endocrine and Metabolic Diseases,
Nutrition, ICAN, Pitié-Salpêtrière Hospital; Assistance Shanghai Institute of Endocrine and Metabolic Diseases,
Publique-Hôpitaux de Paris, CRNH-Ile de France, Paris, Ruijin Hospital Affiliated to Shanghai Jiao Tong University
France. School of Medicine, Shanghai, China.
Agnes Vinet, PhD Laboratoire Pharm-Ecologie Cardiovas- Masao Yoshinaga, MD, PhD Department of Pediatrics,
culaire, UFRip Sciences Technologies Santé, Université National Hospital Organization Kagoshima Medical Center,
d’Avignon et des Pays du Vaucluse, Avignon, France. Kagoshima, Japan.
Vivian E. von Gruenigen, MD Department of Obstetrics and Mauro Zamboni, MD Division of Geriatric Medicine,
Gynecology, Summa Health System, Akron, Ohio, USA. University of Verona, Ospedale Maggiore, Verona, Italy.
Min Xu, MD, PhD Department of Nutrition, Harvard School Valeria Zanandrea, MD Division of Geriatric Medicine,
of Public Health, Boston, MA, USA. University of Verona, Ospedale Maggiore, Verona, Italy.