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 Would you tell us a bit about your educational background and research experiences?

I began my research career with a Ph.D. dissertation about the metabolic effects of legume consumption on protein turnover at the University of Navarra about 30 years ago, which was followed by a postdoctoral stay at Nottingham University (UK), where I investigated the hormonal control of growth.

Both research experiences opened the doors to the future work in obesity research following both basic (cell and animal studies) and applied (human interventions and epidemiological studies) approaches.

 What first drew your interest to the field of obesity, and on what aspects in the field do you focus on specifically?

The focus on obesity came naturally. Indeed, the background concerning metabolism I had previously acquired was essential when I had in my hands many updated methods (analytical, in vivo or in vitro models, facilities for human studies) to investigate the 21st century epidemic.

Also, research funds specifically devoted to research obesity issues—either from national or EU institutions, as well as the continuous support from the University of Navarra—facilitated our initial interest in this highly prevalent condition. Indeed, the two major reasons that drew my attention to obesity were the high burden of obesity for the human being and my background in metabolic knowledge.

 Several of your papers have to do with the Seguimiento Universidad de Navarra (SUN) project. Would you tell us about this project, particularly as it relates to obesity?

The SUN project was launched about 15 years ago as a collaborative initiative between the Department of Preventive Medicine and the Department of Physiology and Nutrition at the University of Navarra.

The research aims are to collect information about dietary and lifestyle habits among former graduates of the University of Navarra (currently more than 20,000) and investigate the impact on chronic diseases with emphasis on diabetes, hypertension, and obesity—the latter being where our department was specifically more interested.

The role of some foods and energy-dense meals on weight gain has also been examined in the SUN Cohort.

 Last year, the SUN project published a paper in Medicine and Science in Sports and Exercise, "Changes in Weight and Physical Activity over Two Years in Spanish Alumni" (Basterra-Gortari F, et al., 41[3]: 516-22, March 2009). What were the findings of this study?

This article concluded that longitudinal changes in leisure activity during follow-up were inversely associated with changes in body weight.

Indeed, this investigation complements previous findings obtained either from the SUN cohort and for the NUGENOB/DIOGENES projects in which sitting hours, low physical activity levels, and sedentary behaviors are related not only to the onset of obesity but also to the poor outcome of a low-energy dietary intervention.

"Obesity is a real challenge for research since many different approaches (in vivo, in vitro, computational modeling, genetic assessment, epidemiological surveys, human intervention trials, etc.) have been applied to understand this public health burden, but the prevalence of this condition is continuously rising worldwide."

These studies concerning physical activity were analyzed by also taking into account the role of dietary macronutrient composition and specific foods (legume, fruit, fish, antioxidants, etc.), which revealed that both aspects of the energy equation (food intake and energy expenditure) should be interpreted together and that not all calories count equally.

 You also have several papers dealing with mitochondrial oxidation and obesity. What has current research told us about the link between these, and what are the implications?

The attraction of mitochondrial involvement in obesity was initially focused on investigating the role of some uncoupling proteins (UCPs) on energy homeostasis as affected by the diet or specific thermogenic agents. Then we became interested in the transfer of UCP genes into the liver, which resulted in the induction of heat-dissipative effects.

Lately, we are devoted to analyzing the role of some specific antioxidants on mitochondrial biogenesis and functions as well as on gene-expression-related studies. These studies will hopefully provide new insights concerning the hypothesis that energy-efficiency processes mediated by the mitochondria are relevant in body-weight regulation.

 Based on your paper list in our analysis, you also have examined the genetic aspect of obesity. Would you tell us about this part of your research?

For many years, obesity was believed to be a problem of sloth, gluttony, and sedentary behaviors, but pioneer reports in the 1920s suggested that some people are more susceptible to excessive weight gain and that fat accumulation may follow a sexually dimorphic pattern (android vs. gynoid models).

Only in the 1970s did the first quantitative genetic studies appear that confirmed that some mutations and specific gene polymorphisms could contribute specifically to the obesity condition.

Our contribution concerned the involvement of some uncoupling molecules (UCPs), adrenoceptors (ADBR2, ADBR3), transcription factors (PPAR), inflammatory mediators (TNF-alpha) and newly described proteins (FTO, etc.) in fuel homeostasis and also genomic markers or predictors of weight loss after following an energy-restricted diet or Mediterranean dietary patterns.

These studies were completed by nutrigenomics approaches where the mRNA levels were assessed to understand the role of the genetic control on body weight homeostasis with a focus on pro-inflammatory and oxidative stress proteins.

 Which are your favorite papers?

This is a nice but difficult question, because I feel that every scientific work has its own "character" when it is a genuine contribution to the advancement of the knowledge.

However, I would like to mention six papers that I consider innovative and challenging, despite the fact that they are not among those that have high citations in the scientific literature:

• The investigation of a possible vaccine against obesity, in De Fanti BA, et al., "Immunoneutralization and anti-idiotype production: two-sided applications of leptin," (Trends Immunol. 23[4]:180-1, April 2002)
• The application of an antifungal to protect against adiposity induced by a high fat diet, in Campion J, Martinez JA, "Ketoconazole, an antifungal agent, protects against adiposity induced by a cafeteria diet," (Horm. Metab. Res. 36[7]:485-91, July 2004)
• The reduction in energy efficiency in liver mitochondria induced by gene transfer, in Gonzalez-Muniesa P, et al., "Reduction in energy efficiency induced by expression of the uncoupling protein, UCP1, in mouse liver mitochondria," (Int. J. Mol. Med. 17[4]:591-7, April 2006)
• The hydrodynamic transfer of two glyoxylate cycle enzyme genes to modify fat-to-glucose interconversion, in Cordero P, et al., "Fat-to-glucose interconversion by hydrodynamic transfer of two glyoxylate cycle enzyme genes," (Lipids Health Dis. 7: art. no. 49, 10 December 2008)
• The impact of oxygen/antioxidants on obesity, in both Quintero P, et al., "Impact of oxygen availability on body weight management" (Medical Hypotheses 74[5]:901-7, May 2010), and Puchau B, et al., "Dietary total antioxidant capacity is negatively associated with some metabolic syndrome features in healthy young adults" (Nutrition 26[5]: 534-41, May 2010).

How far would you say obesity research has come in the past decade? Where do you see it going in the next 10 years?

Obesity is a real challenge for research since many different approaches (in vivo, in vitro, computational modeling, genetic assessment, epidemiological surveys, human intervention trials, etc.) have been applied to understand this public health burden, but the prevalence of this condition is continuously rising worldwide.

In the next few years, I foresee that epigenetics and "omics" technologies will contribute to opening new doors and pave new ways concerning the energy metabolism machinery and to fight effectively against obesity.

J. Alfredo Martinez, Ph.D.
Department of Physiology and Nutrition
University of Navarra
Pamplona, Spain

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J. ALFREDO MARTINEZ'S CURRENT MOST-CITED PAPER IN ESSENTIAL SCIENCE INDICATORS:

Martinez-Gonzalez MA, et al., "Validation of the Spanish version of the physical activity questionnaire used in the Nurses' Health Study and the Health Professionals' Follow-Up Study," Public Health Nutr. 8(7): 920-7, October 2005, with 42 cites. Source: Essential Science Indicators^SM from Clarivate.

KEYWORDS: OBESITY, METABOLISM, EPIDEMIOLOGY, PUBLIC HEALTH BURDEN, SEGUIMIENTO UNIVERSIDAD DE NAVARRA (SUN) PROJECT, DIETARY HABITS, LIFESTYLE, CHRONIC DISEASES, FOODS, BODY WEIGHT, PHYSICAL ACTIVITY, MITOCHONDRIAL OXIDATION, UNCOUPLING PROTEINS, ENERGY HOMEOSTASIS, GENE-EXPRESSION STUDIES, NUTRIGENOMICS.

 

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• J. Alfredo Martinez Interview - Special Topic of Obesity