Abstract
Low-carbohydrate, high-fat (LC-HF) diets are popular for inducing weight loss in overweighed adults. Adaptive thermogenesis increased by specific effects of macronutrients on energy expenditure has been postulated to induce this weight loss. We studied brown adipose tissue (BAT) morphology and function following exposure to different LC-HF diets.MethodsMale Wistar rats were fed a standard control diet ad libitum or pair-fed isoenergetic amounts of three experimental diets for 4 weeks. The diets had the following macronutrient composition (% metabolizable energy: carbohydrates, fat, protein): control (64.3/16.7/19), LC-HF-low protein (LC-HF-LP, 1.7/92.8/5.5), LC-HF-normal-protein (LC-HF-NP, 2.2/78.7/19.1), and a high fat diet with carbohydrates (“high fat”, 19.4/61.9/18.7).ResultsBody weight gain was reduced in all pair-fed experimental groups as compared to rats fed the control diet, with more pronounced effect in rats on LC-HF diets than on the high fat diet with carbohydrates. High fat diets increased expression of PGC1α and ADRB3 in BAT indicating higher SNS outflow. However, UCP1 mRNA expression and expression of UCP1 assessed by immunohistochemistry was not different between diet groups. In accordance, analysis of mitochondrial function in-vitro by extracellular flux analyser (Seahorse Bioscience) and measurement of inducible thermogenesis in vivo (primary endpoint), explored by indirect calorimetry following norepinephrine injection, did not show significant differences between groups. Histology of BAT revealed increased lipid droplet size in rats fed the high-fat diet and both LC-HF diets.ConclusionAll experimental diets upregulated expression of genes which are indicative for increased BAT activity. However, the functional measurements in vivo revealed no increase of inducible BAT thermogenesis. This indicates that lower body weight gain with LC-HF diets and a high fat diet in a pair-feeding setting is not caused by increased adaptive thermogenesis in BAT.
Highlights
Adherence to low carbohydrate-high fat (LC-HF) diets has been associated with higher short term weight loss [1,2] and a more favorable lipid profile [3], than conventional low-fat diets
Using a rat model and a pair-feeding setting, we investigated the effects of macronutrients on body-weight gain, brown adipose tissue and adaptive thermogenesis capacity, which was the major objective of this study
Body weight gain was significantly lower in all rats fed the experimental diets as compared to the control group
Summary
Adherence to low carbohydrate-high fat (LC-HF) diets has been associated with higher short term weight loss [1,2] and a more favorable lipid profile [3], than conventional low-fat diets. Several mechanisms have been suggested to cause weight loss in LC-HF diets: the induction of ketosis and the associated loss of energy via ketone bodies excreted in urine, suppression of appetite due to circulating ketones, or increased energy expenditure due to adaptive thermogenesis [6,7]. These potential mechanisms and the effectiveness of low carbohydrate diets have been questioned [8]. While there is up to now no evidence of increased energy expenditure in humans on a ketogenic diet, increased energy expenditure was demonstrated in mice, but not rats fed a ketogenic diet with ad libitum access to food [10,11]
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