The study of food impact on physiology and health

The broad aim of my research is to fill this gap and to understand the role of nutritional factors during development
November 10, 2019

Janna Zaretsky, Shelley Griess Fishenheimer, Tamara Shmul, Reut Rozner, Roni Sides, Svetta Pen.

The lab for skeletal development - Institute of Biochemistry and Nutrition, Faculty of Agricultural, Food and Environmental Sciences, The Hebrew University.


The link between under-nutrition and growth retardation is well documented. A trend of greater height is recognized in countries where proper nutrition, exercise and healthy life-style are more available. Children from developing countries with Protein-energy malnutrition had significantly lower body weight and height than healthy subjects.

Furthermore, animal studies clearly demonstrate the deleterious effects of nutritional deficiencies on linear growth (1). But what is the reciprocal? What if you eat too much? Are you going to over grow? Yes, it is recognized that overweight children are taller than age-matched, normal-weight children. This tall stature is often associated with an accelerated skeletal maturation and an earlier timing of puberty, but not with the final adult height (2). Nowadays, it is clear that factors such as vitamin D and calcium are just the tip of the iceberg, and the role of nutritional factors in bone development has yet to be elucidated. The broad aim of my research is to fill this gap and to understand the role of nutritional factors during development.
Several studies have been conducted in our lab in order to shed light upon the influence of specific components on bone development. For instance, we have shown that -3 PUFA improve bone growth and bone quality already from embryonic stages, and directly modulates the activity of chondrocytes (3). In addition, we demonstrated the induction of glucose metabolism and subsequent osteo-chondrogenic differentiation and calcification by osteocalcin in a Vitamin D -dependent manner, in-vivo and in-vitro (4, 5). We studied the effect of various metabolic hormones on the development of the young skeleton, and have shown the effects of cytokines secreted from the adipose tissue on bone development and properties (6-9).

Figure 1│ Calcium supplementation of fast-food diet rescues tibial GP structure but results in kidney mineralization. 24 rats were divided randomly into 3 groups. The 1st group (n=8) got a standard diet (Control). The 2nd group (n=8) was given a diet based fast-food including soft drink (FF+CSD). The 3rd group (n=8) received the fast-food diet supplemented with calcium phosphate (FF+CSD+Ca). At the end of the experiment, rats were anesthetized with isofluran, blood samples were collected, and the animals were sacrificed. Their internal organs (kidney) and bones (femur, tibia) were harvested.
a, Total of 12 tibiae were dissected, processed and stained with safranin-O. b, Representative 3-D reconstructions of whole femur scaled for mineral density.  d, Staining of tibial GP for ALP and TRAP activity. e, Total of 16 kidneys were dissected, processed and stained with Alcian von Kossa staining, detecting mineral deposits.


However, nutrition is different; no one eats diet rich only in -3 PUFA. People are eating many types of foods and various diet patterns. A paper published recently in Nature (10) made the observation that "people do not choose nutrients, they select combinations of foods…researchers should be more creative and research funders bolder in assessing the health implications of common combinations of foods". That is precisely what we do, one of the novel aspects of our research is giving rats a “whole diet” as consume by humans. This is an unusual scientific approach, the common nutritional methodology is to add or remove one component at a time from the diet and study its effect separately, as in pharmaceutical or genetic studies. Our study offers a new type of nutritional research methodology, by studying the effects of general dietary patterns rather than the effect of single individual nutrients.
Over the past 30 years, there has been a radical change in eating habits toward processed food (11, 12). This trend leads children to excessive consumption of food and drinks that are high in fat and refined sugars but do not provide the appropriate levels of vitamins and minerals required for growth (13). The acknowledged health outcomes of frequent consumption of processed-food (the modern mal-nutrition) include obesity and numerous metabolic disorders (14). In our recent study, we fed young growing rats with ultra-processed-food and studied its effect on bone development and quality. Rats fed with this diet demonstrated severe bone phenotypes, including cartilaginous lesions in their growth-plates and a sieve-like appearance of the cortical bone. This was accompanied by significant reduction in bone mineral density and reduced mechanical strength to less than half compared to healthy bones (Figure 1). The data highlights a serious implication of ultra-processed-diets during childhood, novel phenotypes which are way beyond the known metabolic effects of such diet.

Figure 2.


Based on our expertise in diet planning and bone analyses, we developed a sensitive physiological preclinical model that can rapidly and confidently address the health issue of different nutrients and diet patterns. Our model is based on the postnatal growth, defined as the gain in body size during the juvenile period. Postnatal skeleton growth is the major parameter for development and health in children, and heavily influenced by consumption of various compounds during the period of rapid growth. Thus, the young rat provides a most sensitive and reliable preclinical model to study minute variation in the diet and observe the quality of the diet.

For instance, in one of our projects we assess the health implication of alternative proteins in the diet. A growing global population place increased pressure on the world’s resources to provide sustainable and healthy food. Particularly, animal-based protein has a negative environmental impact on gas emissions water and land resources.

Thus, conjoining alternative protein sources in the human diet, such as algae, bugs or "artificial meat", is a major challenge, that requires comparisons between novel and existing proteins, in terms of health impacts. We are using this preclinical model to address the effect of different protein sources in the diet on growth, physiology and quality parameters of the skeleton.

The alternative protein sources that tested in equivalent diets are: animal, plant, insects, algae and in-vitro meat. The combined deep understanding and expertise of our lab in diet planning and bone biology, together with the use of gene expression studies (transcriptome), microbiome analyses and computational data mining approach, enable the optimization of future protein alternatives in the diet (Figure 2).