High‐fat diet induced adiposity and insulin resistance in mice lacking the myotonic dystrophy protein kinase

Abstract

a b s t r a c tMyotonic dystrophy 1 (MD1) is caused by a CTG expansion in the 3 0 -unstranslated region of the myotonic dystrophy protein kinase (DMPK) gene. MD1 patients frequently present insulin resistance and increased visceral adiposity. We examined whether DMPK deficiency is a genetic risk factor for highfat diet-induced adiposity and insulin resistance using the DMPK knockout mouse model. We found that high-fat fed DMPK knockout mice had significantly increased body weights, hypertrophic adipocytes and whole-body insulin resistance compared with wild-type mice. This nutrient-genome interaction should be considered by physicians given the cardiometabolic risks and sedentary lifestyle associated with MD1 patients.

Modulation of Gene Expression by 3-Iodothyronamine: Genetic Evidence for a Lipolytic Pattern

“…This gene encodes a serine/threonine protein kinase, whose deficiency appears to be a risk factor for adiposity. Dmpk KO mice fed with high-fat diet exhibit increased body weight and fat mass, due to adipocyte hypertrophy [76].…”

Disruption of Inducible 6-Phosphofructo-2-kinase Ameliorates Diet-induced Adiposity but Exacerbates Systemic Insulin Resistance and Adipose Tissue Inflammatory Response

“…Similarly, after a feeding of HFD for 20 weeks, both of the two different strains of wild-type mice gain a significant increase in fat mass, which is associated with systemic insulin resistance and glucose intolerance (2). A recent study even indicates that feeding an HFD to mice for only 6 weeks is sufficient to induce adiposity and systemic insulin resistance (3). Furthermore, as documented in mice lacking the myotonic dystrophy protein kinase, a larger augmentation in adiposity is accompanied by a greater increase in the severity of systemic insulin resistance (3).…”

“…Furthermore, as documented in mice lacking the myotonic dystrophy protein kinase, a larger augmentation in adiposity is accompanied by a greater increase in the severity of systemic insulin resistance (3). Because of this, adiposity has been generally viewed as an important contributor of systemic insulin resistance (3)(4)(5)(6)(7). On the other hand, reducing adiposity has been considered as an effective way to reverse systemic insulin resistance (1,8).…”

“…A recent study even indicates that feeding an HFD to mice for only 6 weeks is sufficient to induce adiposity and systemic insulin resistance (3). Furthermore, as documented in mice lacking the myotonic dystrophy protein kinase, a larger augmentation in adiposity is accompanied by a greater increase in the severity of systemic insulin resistance (3). Because of this, adiposity has been generally viewed as an important contributor of systemic insulin resistance (3)(4)(5)(6)(7).…”

“…As demonstrated by numerous data generated from high fat diet (HFD) 3 -fed rodents, overnutrition is associated with adiposity and systemic insulin resistance. For example, feeding an HFD to rats for 10 weeks causes a significant increase in visceral fat mass, which is accompanied by a decrease in systemic insulin sensitivity as evidenced by decreased rate of clamp glucose infusion (1).…”