Isoenergetic Feeding of Low Carbohydrate-High Fat Diets Does Not Increase Brown Adipose Tissue Thermogenic Capacity in Rats

PLOS ONE, Dec 2019

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. Methods Male 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). Results Body 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. Conclusion All 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.

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Isoenergetic Feeding of Low Carbohydrate-High Fat Diets Does Not Increase Brown Adipose Tissue Thermogenic Capacity in Rats

et al. (2012) Isoenergetic Feeding of Low Carbohydrate-High Fat Diets Does Not Increase Brown Adipose Tissue Thermogenic Capacity in Rats. PLoS ONE 7(6): e38997. doi:10.1371/journal.pone.0038997 Isoenergetic Feeding of Low Carbohydrate-High Fat Diets Does Not Increase Brown Adipose Tissue Thermogenic Capacity in Rats Matthias J. Betz 0 Maximilian Bielohuby 0 Brigitte Mauracher 0 William Abplanalp 0 Hans- 0 Helge Mu ller 0 Korbinian Pieper 0 Juliane Ramisch 0 Matthias H. Tscho p 0 Felix Beuschlein 0 Martin Bidlingmaier 0 Marc Slawik 0 Marcia B. Aguila, State University of Rio de Janeiro, Biomedical Center, Institute of Biology, Brazil 0 1 Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der LMU, Munich, Germany, 2 Department of Medicine, Metabolic Diseases Institute, University of Cincinnati, Cincinnati, Ohio, United States of America, 3 Institute for Medical Informatics , Biometry and Epidemiology , Ludwig-Maximilians University , Munich, Germany , 4 Clinic of Small Animal Surgery and Reproduction, Centre of Clinical Veterinary Medicine, Ludwig-Maximilians University , Munich, Germany , 5 Institute for Diabetes and Obesity, Helmholtz Centre for Health and Environment and Technical University , Munich , Germany 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. Methods: Male 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-HFNP, 2.2/78.7/19.1), and a high fat diet with carbohydrates (''high fat'', 19.4/61.9/18.7). Results: Body 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 PGC1a 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. Conclusion: All 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. - . These authors contributed equally to this work. 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. Although more recent studies did not detect a significantly lower body weight after long-term intake of low-carbohydrate, high-fat diets compared to those with low-fat and normal carbohydrate content [4,5], low carbohydrate diets enjoy unaltered popularity. 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]. However, these potential mechanisms and the effectiveness of low carbohydrate diets have been questioned [8]. Moreover, we have recently shown that the loss of energy via excretion of ketone bodies is quantitatively negligible in rats fed a ketogenic diet and does not contribute substantially to overall energy expenditure [9]. In addition, ketosis was not associated with weight loss in humans [1]. 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]. Brown adipose tissue (BAT) is a metabolically highly active tissue with the unique capability to dissipate chemical energy into Table 1. Primer sequences (59-39). CGATCACCATATTCCAGGTCAAG CCCAGAGCATGGTGCCTTCGC AGGCTGCAGCGCTAAATTCATCT AGGTGAGGTCTGCCACAAGT CGAGCCAAGATGGTGAGTTCGACA GGGAGGTAGTGACGAAAAATAACAA (...truncated)


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Matthias J. Betz, Maximilian Bielohuby, Brigitte Mauracher, William Abplanalp, Hans-Helge Müller, Korbinian Pieper, Juliane Ramisch, Matthias H. Tschöp, Felix Beuschlein, Martin Bidlingmaier, Marc Slawik. Isoenergetic Feeding of Low Carbohydrate-High Fat Diets Does Not Increase Brown Adipose Tissue Thermogenic Capacity in Rats, PLOS ONE, 2012, Volume 7, Issue 6, DOI: 10.1371/journal.pone.0038997