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

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.

Interleukin 6 Deficiency Modulates the Hypothalamic Expression of Energy Balance Regulating Peptides during Pregnancy in Mice

“…Additional mechanisms might include a decrease in energy expenditure in pregnant Il6 deficient mice in comparison to WT controls as a result of an altered BAT functionality. This option seems plausible in light of the decreased UCP3 levels and the accumulation of lipid droplets observed in the BAT of Il6 -KO mice at mid pregnancy, which suggests a reduction in the BAT thermogenic program in our model [55].…”

Impact of fasting time on hepatic lipid metabolism in nutritional animal studies

“…9,10,23) In pair-feeding conditions, eating patterns can be different among groups. If animals are killed at Notes: Rats were fed an AIN-93G semisynthetic diet for 2 wk.…”

Sustained exposure to diets with an unbalanced macronutrient proportion alters key genes involved in energy homeostasis and obesity-related metabolic parameters in rats

“…Other group has previously reported the lack of the effect of isocaloric HF feeding on UCP1 expression and thermogenic capacity. 28 High caloric intake and HF diet intake independent of caloric intake are known to stimulate the sympathetic nervous system activity which controls UCP1-mediated thermogenesis. 28 Thus, probably, the fact that the HF diet was administered under isocaloric conditions without increased caloric intake produced a not so potent UCP1 induction.…”

“…28 High caloric intake and HF diet intake independent of caloric intake are known to stimulate the sympathetic nervous system activity which controls UCP1-mediated thermogenesis. 28 Thus, probably, the fact that the HF diet was administered under isocaloric conditions without increased caloric intake produced a not so potent UCP1 induction. However, we cannot discard the effect on thermogenesis, as it has been reported that isocaloric HF feeding in rats induces BAT thermogenesis by augmenting the activation of UCP1 rather than its expression.…”