A putative low-carbohydrate ketogenic diet elicits mild nutritional ketosis but does not impair the acute or chronic hypertrophic responses to resistance exercise in rodents

Abstract

We examined whether acute and/or chronic skeletal muscle anabolism is impaired with a low-carbohydrate diet formulated to elicit ketosis (LCKD) vs. a mixed macronutrient Western diet (WD). Male Sprague-Dawley rats (9-10 wk of age, 300-325 g) were provided isoenergetic amounts of a LCKD or a WD for 6 wk. In AIM 1, basal serum and gastrocnemius assessments were performed. In AIM 2, rats were resistance exercised for one bout and were euthanized 90-270 min following exercise for gastrocnemius analyses. In AIM 3, rats voluntarily exercised daily with resistance-loaded running wheels, and hind limb muscles were analyzed for hypertrophy markers at the end of the 6-wk protocol. In AIM 1, basal levels of gastrocnemius phosphorylated (p)-rps6, p-4EBP1, and p-AMPKα were similar between diets, although serum insulin (P < 0.01), serum glucose (P < 0.001), and several essential amino acid levels (P < 0.05) were lower in LCKD-fed rats. In AIM 2, LCKD- and WD-fed rats exhibited increased postexercise muscle protein synthesis levels (P < 0.0125), but no diet effect was observed (P = 0.59). In AIM 3, chronically exercise-trained LCKD- and WD-fed rats presented similar increases in relative hind limb muscle masses compared with their sedentary counterparts (12-24%, P < 0.05), but there was no between-diet effects. Importantly, the LCKD induced "mild" nutritional ketosis, as the LCKD-fed rats in AIM 2 exhibited ∼1.5-fold greater serum β-hydroxybutyrate levels relative to WD-fed rats (diet effect P = 0.003). This study demonstrates that the tested LCKD in rodents, while only eliciting mild nutritional ketosis, does not impair the acute or chronic skeletal muscle hypertrophic responses to resistance exercise.

A Ketogenic Diet in Rodents Elicits Improved Mitochondrial Adaptations in Response to Resistance Exercise Training Compared to an Isocaloric Western Diet

“…This observation could be a result of increased AMPK activation, an important signaling event in mitochondrial biogenesis and function (Kennedy et al, 2007), induced by KD. However, previous report on these animals observed no differences in p-AMPK (Roberts et al, 2016). This observation was attributed to adaptation to the ketogenic diet and a resetting of AMPK signaling, thus the differences in significance from our current findings may be due to adaptations earlier in training while adaptation to the KD was taking place (Roberts et al, 2016).…”

“…Furthermore, animals exposed to resistance wheel exercise training had increases in mitochondrial complex activity, mRNA expression of genes involved in metabolism, and endogenous antioxidant protein expression. Previous observation on the hypertrophic response of these animals by Roberts et al demonstrated increased markers of ketogenesis indicating that KD-fed animals expressed “mild” ketosis (Roberts et al, 2016). …”

“…During acclimation, animals were provided standard rodent chow (24% protein, 58% CHO, 18% fat; 114 Teklad Global #2018 Diet, Harlan Laboratories) and water ad libitum in a maintained ambient temperature and constant 12 h light: 12 h dark cycle. The animals for this study were the same animals previously published by Roberts et al (2016) who reported that KD and WD feeding promoted similar increases in muscle mass with the employed resistance-loaded running wheel regimen.…”

A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice

“…In skeletal muscle, the KD increased p-4E-BP1 levels. Similarly, a recent study in rats fed a relatively high protein (~20% kcal) ketogenic diet detected no change in p-rpS6 and a trend towards an increase in p-4E-BP1 (Roberts et al, 2016). Thus, protein level may have a major influence on mTORC1 signal in response to a KD.…”

Low-Carbohydrate-High-Fat Diet: Can it Help Exercise Performance?

“…These changes are at least partially due to reduced anti-lipolytic insulin action and protein-protective action of increased total and free thyroxine index after a LCHF diet (Volek et al, 2002). Furthermore, a LCHF diet led to a similar magnitude increase in the muscle protein synthesis rate, activation of AMP-activated protein kinase and 4E-binding protein-1 compared to a HCLF diet after resistance exercise in rats (Roberts et al, 2016). Therefore, it is possible that LCHF diets, in combination with resistance training, can maintain fat-free mass while receiving the benefit of loss in fat mass and body weight.…”