Reciprocal Compensation to Changes in Dietary Intake and Energy Expenditure within the Concept of Energy Balance

An imbalance between energy intake and energy expenditure is the primary etiology for excess weight gain. Increased energy expenditure via exercise and energy restriction via diet are commonly used approaches to induce weight loss. Such behavioral interventions, however, have generally resulted in a smaller than expected weight loss, which in part has been attributed to compensatory adaptations in other components contributing to energy balance. Current research points to a loose coupling between energy intake and energy expenditure on a daily basis, and evidence for long-term adaptations has been inconsistent. The lack of conclusive evidence on compensatory adaptations in response to alterations in energy balance can be attributed to differences in intervention type and study population. Physical activity (PA) levels may be reduced in response to aerobic exercise but not in response to resistance exercise. Furthermore, athletic and lean adults have been shown to increase their energy intake in response to exercise, whereas no such response was observed in obese adults. There is also evidence that caloric restriction is associated with a decline in PA. Generally, humans seem to be better equipped to defend against weight loss than avoid weight gain, but results also show a large individual variability. Therefore, individual differences rather than group means should be explored to identify specific characteristics of “compensators” and “noncompensators.” This review emphasizes the need for more research with simultaneous measurements of all major components contributing to energy balance to enhance the understanding of the regulation of energy balance, which is crucial to address the current obesity epidemic.     

Bile Acids and GPBAR-1: Dynamic Interaction Involving Genes,Environment and Gut Microbiome

Bile acids (BA) are amphiphilic molecules synthesized in the liver from cholesterol. BA undergo continuous enterohepatic recycling through intestinal biotransformation by gut microbiome and reabsorption into the portal tract for uptake by hepatocytes. BA are detergent molecules aiding the digestion and absorption of dietary fat and fat-soluble vitamins, but also act as important signaling molecules via the nuclear receptor, farnesoid X receptor (FXR), and the membrane-associated G protein-coupled bile acid receptor 1 (GPBAR-1) in the distal intestine, liver and extra hepatic tissues. The hydrophilic-hydrophobic balance of the BA pool is finely regulated to prevent BA overload and liver injury. By contrast, hydrophilic BA can be hepatoprotective. The ultimate effects of BA-mediated activation of GPBAR-1 is poorly understood, but this receptor may play a role in protecting the remnant liver and in maintaining biliary homeostasis. In addition, GPBAR-1 acts on pathways involved in inflammation, biliary epithelial barrier permeability, BA pool hydrophobicity, and sinusoidal blood flow. Recent evidence suggests that environmental factors influence GPBAR-1 gene expression. Thus, targeting GPBAR-1 might improve liver protection, facilitating beneficial metabolic effects through primary prevention measures. Here, we discuss the complex pathways linked to BA effects, signaling properties of the GPBAR-1, mechanisms of liver damage, gene-environment interactions, and therapeutic aspects.     

Development of Infrared Imaging to Measure Thermogenesis in Cell Culture: Thermogenic Effects of Uncoupling Protein-2, Troglitazone,and β-Adrenoceptor Agonists

Purpose. Although the effects of thermogenic agents in cell culture can be measured by direct microcalorimetry, only a few samples can be analyzed over several hours. In this report, we describe a robust non-invasive technique to measure real-time thermogenesis of cells cultured in microtiter plates using infrared thermography. Methods. Yeast were transformed with uncoupling protein-2 (UCP2) or exposed to carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) or rotenone. Adipocytes were exposed to rotenone, FCCP, cycloheximide, troglitazone, or CL316243. Thermogenesis was measured using infrared thermography. Results. Thermogenesis increased after exposing yeast to the mitochondrial uncoupler, FCCP, or transforming the cells with UCP2. Further, thermogenesis in adipocytes was stimulated by CL316243, a ₃-adrenoceptor agonist being developed to treat obesity. The protein synthesis inhibitor, cycloheximide, did not inhibit CL316243-mediated thermogenesis. In contrast, the mitochondrial proton transport inhibitor, rotenone, inhibited thermogenesis in yeast and adipocytes. Similarly, the antidiabetic agent, troglitazone, suppressed thermogenesis in adipocytes. Although increased UCP synthesis resulted in increased thermogenesis in yeast, UCP expression did not correlate with thermogenesis in adipocytes. Conclusions. The results, taken together with the high resolution (0.002°C) and robustness (384-well format) of the approach, indicate infrared-imaging is a rapid and effective method for measuring thermogenesis in vitro.     

Short photoperiod enhances thermogenic capacity in Brandt's voles

Environmental cues play important roles in the regulation of an animal's physiology and behavior. In the present study, we examined the effects of short photoperiod (SD) on body weight as well as on several physiological, hormonal, and biochemical measures indicative of thermogenic capacity to test our hypothesis that short photoperiod stimulates increases in thermogenesis without cold stress in Brandt's voles. SD voles showed increases in basal metabolic rate (BMR) and nonshivering thermogenesis (NST) during the 4-week photoperiod acclimation. At the end, these voles (SD) had lower body weights, higher levels of cytochrome C oxidase (COX) activity and mitochondrial uncoupling protein-1 (UCP1) contents in brown adipose tissues (BAT), and higher concentrations of serum tri-iodothyronine (T3) and thyroxine (T4) compared to LD voles. No differences were found between male and female voles in any of the above-mentioned measurements. Together, these data indicate that SD experience enhances thermogenic capacity similarly in males and females of Brandt's voles.     

Pyrazolone derivative C29 protects against HFD-induced obesity in mice via activation of AMPK in adipose tissue

Beige adipocytes have been considered as a potential strategy in anti-obesity therapy because of its thermogenic capacity. AMP-activated protein kinase (AMPK) plays important roles in regulating adipose tissue function. C29 is a novel pyrazolone derivative with AMPK activity. In the current study, we investigated the role of C29 in the regulation of thermogenesis using differentiated adipocytes and diet-induced obese mice, and explored the mechanisms that might be involved in energy expenditure via adipocyte AMPK activation. We showed that treatment with C29 (2.5–10 μM) concentration-dependently increased thermogenesis in differentiated preadipocytes separated from inguinal white adipose tissue (iWAT), evidenced by increased expression levels of thermogenesis markers such as Ucp1, Pgc-1α, Dio2, Prdm16, Cox7a1, Cox8b, Elovl3, and Cidea, fatty acid oxidation (FAO) genes including Cpt1a, Lcad and Pparα, as well as beige-selective genes such as Cd137, Tmem26, Slc27a1, and Tbx1. In high-fat diet (HFD)-fed mice, oral administration of C29 (30 mg·kg⁻¹·day⁻¹) for 9 weeks alleviated HFD-induced obesity, promoted energy expenditure and modulated iWAT browning. However, these effects were not observed in adipose-specific AMPKα1/α2 knockout (AKO) mice following C29 administration. Together, this study demonstrates that C29 regulates energy balance via adipocyte AMPK. Our findings show that the discovery of AMPK activators that specifically target adipose tissue may have therapeutic potential for treating obesity-related metabolic diseases.     

Effects of Dietary Protein Source and Quantity during Weight Loss on Appetite,Energy Expenditure,and Cardio-Metabolic Responses

Higher protein meals increase satiety and the thermic effect of feeding (TEF) in acute settings, but it is unclear whether these effects remain after a person becomes acclimated to energy restriction or a given protein intake. This study assessed the effects of predominant protein source (omnivorous, beef/pork vs. lacto-ovo vegetarian, soy/legume) and quantity (10%, 20%, or 30% of energy from protein) on appetite, energy expenditure, and cardio-metabolic indices during energy restriction (ER) in overweight and obese adults. Subjects were randomly assigned to one protein source and then consumed diets with different quantities of protein (4 weeks each) in a randomized crossover manner. Perceived appetite ratings (free-living and in-lab), TEF, and fasting cardio-metabolic indices were assessed at the end of each 4-week period. Protein source and quantity did not affect TEF, hunger, or desire to eat, other than a modestly higher daily composite fullness rating with 30% vs. 10% protein diet (p = 0.03). While the 20% and 30% protein diets reduced cholesterol, triacylglycerol, and APO-B vs. 10% protein (p < 0.05), protein source did not affect cardio-metabolic indices. In conclusion, diets varying in protein quantity with either beef/pork or soy/legume as the predominant source have minimal effects on appetite control, energy expenditure and cardio-metabolic risk factors during ER-induced weight loss.     

Energy cost of physical activity in patients with anorexia nervosa

To assess the amount of energy cost for a standardized physical activity, activity‐induced thermogenesis (AIT) was measured in eight hyperactive and eight sedentary patients with anorexia nervosa as well as in 14 sport students and 14 sedentary controls. Resting metabolic rate (RMR) and AIT were measured by indirect calorimetry. RMR was measured after an overnight fast and began 20 min after the placement of the hood and lasted for 20 min. For the next 10 min subjects had to ride a recumbent bicycle ergometer (25 W) and AIT was measured. Absolute RMR in both anorectic groups was significantly lower than in both normal weight groups, but after adjusting for lean body mass (LBM) RMR did not differ among the groups. Absolute AIT was significantly lower in hyperactive anorectic patients and in sport students compared to the controls. After adjusting for LBM AIT was still significantly lower in the hyperactive anorectic group and in the group of sport students compared to the control group. These results indicate that despite severe underweight and biological changes in muscles anorectic patients still have an energy sparing metabolism during moderate physical activity. Copyright © 2000 John Wiley & Sons, Ltd and Eating Disorders Association.