This 2015 Indiana rodent study found:
“DNA damage is a root cause of adipocyte senescence [fat cells that can no longer replicate], which plays a determining role in the development of obesity and insulin resistance.”
The researchers removed the capability for the subject mice to produce a protein that “plays an essential role in preventing cutaneous cancer caused by UV radiation-induced DNA damage.” They showed that this genetic deficiency:
“Causes obesity with visceral fat accumulation, hepatic steatosis, hyperleptinemia, hyperinsulinemia, and glucose intolerance.”
These researchers – in contrast with the Pulling on the chain of causes and effects with insulin resistance study – investigated causes for the various effects that included insulin resistance. However, the study’s applicability to humans wasn’t clear, since we most often develop symptoms such as insulin resistance due to causes other than genetics.
The study also demonstrated that treatment with a common dietary supplement – N-acetyl cysteine (NAC) – or metformin (Met):
“Reduce[d] adipose DNA damage.
Ameliorated cellular senescence and metabolic abnormalities.”
High-fat and high-fructose diets caused the opposite effects in the subject genetic-deficient mice.
http://www.pnas.org/content/112/33/E4556.full “Ablation of XP-V gene causes adipose tissue senescence and metabolic abnormalities”