Carbohydrates, proteins and lipids are the main energy-producing components of food and are essential nutrients for all animals. After ingesting food, life will metabolize a large number of nutrients, and metabolic pathways are highly conserved in the evolutionary process. For example, glycolysis is the first step in glucose breakdown and is conserved in almost all eukaryotic and prokaryotic cell types.
However, closely related species, populations, and individuals can show large differences in dietary structure and tolerance to different diets. Perhaps this will remind us of what we call "easy to lose weight" and "easy to fat body" every day. Even though humans have highly conserved metabolic pathways, the prevalence of metabolic diseases such as type 2 diabetes varies considerably between populations and ethnic groups. Some researchers have found that certain genes associated with metabolic pathways are closely linked to metabolic diseases.
This month, the journal Nature Communications published a new international collaborative study in which researchers from Australia, Denmark and Finland studied changes in macronutrient tolerance in Drosophila nigricans. Studies have found that tiny genetic differences affect the ability of fruit flies to harness energy from a variety of nutrients. Fruit-bellied flies show significant genetic differences in survival rates in different diets, especially in high-sugar diets.
Drosophila melanogaster is an important model organism in the study of nutritional and metabolic diseases. It can be used to identify gene-environment interactions in controlled experiments. Because, like humans, fruit flies can also develop obesity and insulin resistance due to high-sugar and high-fat diets. And the molecular mechanisms of these metabolic diseases are highly conserved. For the study, the researchers used 196 different species of drosophila black-bellied flies as subjects and set up 6 dietary patterns (pictured below): high protein (HPD), high sugar (HSD), high fat coconut oil (HFDcoco), high fat lard (HFDlard), Western style (WD), and high starch (HStD).
Figure Note: Figure a shows the main flow of the experiment. b Chart shows the survival of 196 DRFF flies from the pupal stage (pupal) and adult (feathering) in six diets. c Figure shows the standardized survival period.
The researchers found that different isogenic strains from the same starting population had different survival abilities under different dietary conditions, suggesting that genetic components determine tolerance to different macronutrients. Fruit fly survival varies the most in high-sugar and high-coconut oil diets, while most species of drosophila black-bellied flies thrive in high-protein, high-lard, and high-starch diets. High protein and high starch have the same survival rate in different species. The two diets with the lowest survival rates are high-sugar and high-fat coconut oil diets, with 76% and 67% of drosophila surviving to pupate, respectively. However, some species of Drosophila have low survival rates in high-protein and high-starch diets, but relatively high in high-fat lard, high-fat coconut oil, and high-sugar diets.
Illustration: Figure a is a schematic diagram of functional verification screening. Table b shows the number of genes associated with changes in survival, the number of genes tested in the functional verification screening, and the number of genes verified in the screening. c figure shows the relative pupae and feathering (HSD/HPD) of candidate genes.
Studies have also found that coconut oil is harmful to the development of fruit flies. The researchers performed functional in vivo screening and validated 13 high-fat coconut oil genes. Most control flies have a reduced survival rate in a high coconut oil diet, suggesting that coconut oil may adversely affect the development and survival of fruit flies. In contrast, a high lard diet appears to favor development, leading to relatively rapid pupal pupae and good overall survival.
The study eventually found that nearly all of the identified human homologs were associated with type 2 diabetes, most of the genes were associated with changes in BMI and waist circumference, and a large number of genes were also associated with fasting blood glucose. For example, variants of TNIK, the human homolog closest to malformations, have been linked to type 2 diabetes, fasting blood glucose, and BMI. Although some human GWAS studies have shown that many of these genes are associated with type 2 diabetes, the mechanisms by which these genes regulate metabolism and/or the development of metabolic diseases in humans are often unclear. The results here provide a roadmap for revealing the mechanistic role of these genes in the development of metabolic diseases.
Most human homologous genes are associated with type 2 diabetes-related traits.
In summary, the survival rate of Drosophila melabenia in different diets, especially in high-sugar diets, shows significant genetic differences. Genetic analysis and functional validation of the study identified several macronutrient tolerance regulators, including CG10960/GLUT8, Pkn, and Eip75B. The researchers also demonstrated the role of the JNK pathway in glucose tolerance and nascent lipogenesis. And a conservative orphan nuclear hormone receptor tailless has been reported to regulate glucose metabolism through insulin-like peptide secretion and sugar-reactive CCHamide-2 expression. The study supports the application of nutritional genomics in personalized nutrition development
The researchers say further research is still needed, but most of the findings in fruit flies could also be applied to humans. The researchers note that the study provides concrete evidence that the same dietary advice doesn't necessarily work for everyone.
References:
1. Havula, E., et al. "Genetic variation of macronutrient tolerance in Drosophila melanogaster." Nature Communications 13.1 (2022): 1-16.
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