A really interesting study, which covers two very controversial topics in a single experiment. First, whether environmental experiences by an organism can be passed on to offspring without genetic changes in the parent organism. Second, whether low-carb diets are healthy. I think the study clearly demonstrated that the answer to the first question/topic is a resounding YES (corroborated by prior studies with similar findings), while the answer to the second question/topic is a resounding NO. Namely, feeding (mouse) fathers a low-carb-high-fat (LCHF) diet for just 2 weeks resulted in metabolic syndrome, obesity, and even outright diabetes II in their offspring, despite the mothers being perfectly healthy and young. Feeding the fathers a high-carb-low-fat (HCLF) diet did not result in such negative features pass on to the offspring, and in fact reversed the insulin resistance in the fathers induced by the LCHF diet. Finally, the negative offspring effects of feeding LCHF diets to fathers were confirmed in humans as well. Just as importantly, the LCHF diet did not induce obesity in the fathers despite inducing insulin resistance. So, the health effects of low-carb diets on organisms cannot really be judged by external appearance alone, and even if those organisms appear of normal weight, their health may still be compromised enough by the diet to result in heritable, full-blown diabetes in their offspring.
Btw, for people that doubt the diet composition, please see the links below that describe the exact diets used in the study. The first link is the LCHF, and the second link is the HCLF. The changes in carbohydrate percentage in the diet were compensated for by changed in the fat percentage in the diet, while the protein concentrations were the same in both diets.
https://researchdiets.com/formulas/D12492i
https://researchdiets.com/formulas/d12450B
https://pubmed.ncbi.nlm.nih.gov/26721680/
https://www.nature.com/articles/s41586-024-07472-3
“…For eHFD treatment, 6-week-old male mice were randomly assigned to two groups fed for 2 weeks with purified HFD (rodent diet with 60 kcal% from fat; Research Diet D12492i) or LFD control diet (rodent diet with 10 kcal% from fat; Research Diet D12450B) and subsequently mated with a single unexposed, virgin female of the same age. For sHFD treatment, 6-week-old male mice were randomly assigned to two groups fed for 2 weeks with purified HFD (rodent diet with 60 kcal% from fat; Research Diet D12492i) or LFD control diet (rodent diet with 10 kcal% from fat; Research Diet D12450B), mated with a single unexposed virgin female (to empty the epididymis) and moved back to a standard chow diet for 4 weeks. These animals were subsequently mated with a single, virgin and aged-matched female to generate the offspring cohort.”
“…A 2-week exposure to HFD is sufficient to induce a small but significant increase in body weight and adiposity (Extended Data Fig. 2a,c) and reduce whole-body glucose tolerance (Extended Data Fig. 2b,d) in exposed mice. Both phenotypes are reversed by 4 weeks of dietary restoration (Extended Data Fig. 2c,d, chow diet).”
As far as the mechanisms of action of the LCHF diet – it induced mitochondrial dysffunction and that dysfunction was passed on to the offspring.
“… Sperm sncRNA sequencing of mice mutant for genes involved in mitochondrial function, and metabolic phenotyping of their wild-type offspring, suggest that the upregulation of mt-tsRNAs is downstream of mitochondrial dysfunction…Our data support a model by which acute HFD exposure induces mitochondrial dysfunction in somatic tissues and spermatozoa, in which it is compensated by an upregulation of mtDNA transcription.”
https://www.nature.com/articles/d41586-024-01623-2
“…Studies have shown that mothers can pass on metabolic traits to their offspring. As for fathers, Qi Chen, a reproductive-biology researcher at the University of Utah School of Medicine in Salt Lake City, and his team showed in 2016 that fertilized mouse eggs injected with sperm RNA from dads on a high-fat diet developed into mice with metabolic disorders2. Research shows that the ripple effects of a parent’s diet are caused by changes not to the offspring’s genome but to their ‘epigenome’ — the collection of chemical tags hanging from DNA and its associated proteins.”
“…A dad’s sperm records his diet — and this record affects his sons’ metabolism, according to a study of mice and humans1. Giving male mice a high-fat diet raises levels of some types of RNA in their sperm, the study found. The research also showed that the male offspring of male mice on this unhealthy diet had metabolic problems such as glucose intolerance, a characteristic of diabetes. The sons of human dads with a high body mass index (BMI) exhibited similar problems, according to epidemiological analysis.” “…For the Nature study, male mice ate a high-fat diet for two weeks. The study’s authors found that this regimen led to changes in a type of RNA in the sperm’s mitochondria — the structures inside cells that generate energy. The affected molecules, called transfer RNAs, are intermediate products in the process of transcribing DNA into proteins.”
“…The results make sense: a high-fat diet stresses mitochondria, says Raffaele Teperino, lead author of the study and an environmental-epigenetics researcher at Helmholtz Center Munich in Neuherberg, Germany. When stressed, mitochondria make more RNA to produce more energy.”
“…Chen says the study means that, if you make sperm, “you should eat healthy. It will affect the information carried in your sperm. It will affect your offspring”.”
