Wijers 2011 Thesis
| Wijers SLJ (2011) Cold and diet induced thermogenesis in humans: Implications for obesity. Thesis University of Maastricht, NUTRIM School for Nutrition, Toxicology and Metabolism, 174pp. |
Wijers SLJ (2011) Thesis
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Summary The amount of the population suffering from overweight and obesity is rising worldwide. Health problems coinciding with this global weight gain are becoming increasingly serious. To prevent these problems it is a necessity to find effective ways of losing weight and remaining weight stable. In the end, it is necessary to make sure long--]term energy expenditure is higher than or equal to energy intake. Weight loss methods in which energy intake is restricted seem to have only limited long--]term effects in a large part of the population. Therefore, it is of interest to look at the other side of the balance: energy expenditure.
In this thesis, studies investigating the phenomena cold and diet induced adaptive thermogenesis are described: the increase in energy expenditure in response to temperature changes or food intake. By increasing energy expenditure after cold exposure, resulting in additional heat production, an organism is protected against hypothermia. By increasing energy expenditure after overfeeding, less calories are stored and energy balance is better maintained. In CHAPTER 2, the current evidence related to these phenomena is reviewed. Mitochondrial uncoupling seems to be the process that is responsible for adaptive thermogenesis. In the mitochondria, the energy factories of the cell, energy released with combustion of the macronutrients is stored initially as a proton gradient across a membrane. Subsequently, this stored energy is used to convert ADP into ATP, mediated by the enzyme ATP synthase. ATP is the energy carrier used as fuel in cellular processes. Mitochondrial uncoupling makes the conversion of ADP into ATP less efficient, because protons flow back across the mitochondrial membrane, bypassing ATP synthase. In this way, additional heat is produced. This can take place in skeletal muscle tissue, or in brown adipose tissue. Contrary to white adipose tissue, brown adipose tissue does not store fat, but produces heat. Other possible processes involved in adaptive thermogenesis are calcium and substrate cycling, and protein turnover. In these processes, ATP is used to produce heat, instead of being used for other processes in the cells. Mitochondrial uncoupling in skeletal muscle tissue is the foremost mechanism studied in this thesis.
CHAPTER 3 describes two studies on energy expenditure upon mild cold exposure and during overfeeding in the same subjects. For this reason, thirteen subjects stayed three times in a respiration chamber: 1) 36 h at 22 ‹C with normal food intake (control situation); 2) 84 h at 16 ‹C with normal food intake (mild cold); 3) 84 h at 22 ‹C with 1.6 times normal food intake (overfeeding). In a respiration chamber, O2 consumption and CO2 production can be measured. From these data, energy expenditure can be calculated. Cold induced adaptive thermogenesis is the difference in energy expenditure between visit 2 and 1. Diet induced adaptive thermogenesis is the difference in energy expenditure between visit 3 and 1. The increase in energy expenditure upon mild cold exposure and overfeeding was modest, but the interindividual differences were large. Some subjects increased daily energy expenditure with almost 15%, whereas others did not show an increase in energy expenditure at all. Remarkably, the individual metabolic responses to mild cold exposure and overfeeding were significantly related, implicating a shared mechanism. Changes in norepinephrine concentrations were related to the increases in energy expenditure, suggesting involvement of the sympathetic nervous system.
CHAPTER 4 shows that mitochondrial uncoupling in skeletal muscle tissue indeed has a relationship with cold induced adaptive thermogenesis. To investigate this, eleven subjects were exposed to 16 °C for three days. Subsequently a muscle biopsy was taken to measure mitochondrial uncoupling. These tests are performed by measuring O2 consumption of individual muscle fibers with subsequently blocking ATP synthase. All O2 consumption still left, is due to mitochondrial uncoupling. As we expected, after three days of cold exposure, the increase in energy expenditure was related to the increase of skeletal muscle mitochondrial uncoupling.
Next, it was studied which functional proteins are involved in adaptive thermogenesis (CHAPTER 5). This has been investigated using so called proteomic techniques in small pieces of skeletal muscle tissue. The proteins that are present in the muscle tissue can be identified, including the amount and the change in abundance upon the intervention. The amounts of proteins available can be related to the increase in energy expenditure after cold exposure or overfeeding. These tests show that different proteins are active upon cold exposure than upon overfeeding, although glycolysis seems to be the most prominently activated pathway in both interventions.
CHAPTER 6 deals with the thermogenic effect of mild cold exposure in both lean and obese subjects. Obese subjects did not increase energy expenditure significantly, while lean subjects increased energy expenditure on average. Body temperature data indicated that this difference could be attributed to a larger tissue (fat)insulation and/or lower surface to volume ratio in the obese subjects. Interestingly, individual increases in energy expenditure were related to changes in physical activity, although a general decrease in physical activity was observed. This means that an increase in energy expenditure is not simply caused by an increase in physical activity.
To gain more insight in the regulation of adaptive thermogenesis, in CHAPTER 7 a study showing the effect of blocking beta-receptors of the sympathetic nervous system on cold induced adaptive thermogenesis in lean subjects is described. These receptors are proposed to be involved in adaptive thermogenesis. Noteworthy, cold induced adaptive thermogenesis did not decrease when beta-adrenergic receptors were blocked. Nevertheless, the relation between cold induced adaptive thermogenesis and the change in skeletal muscle mitochondrial uncoupling disappeared. The most plausible explanation is that propranolol, the beta-blocker used in this study, does inhibit beta1- and beta2-receptors to a larger extent than beta3-receptors. Therefore, the results indicate that when the beta1- and beta2-receptors are blocked by propranol a beta3-regulated process like mitochondrial uncoupling in brown adipose tissue might take over the role of skeletal muscle mitochondrial uncoupling.
The research presented in this thesis shows that adaptive thermogenesis is potentially an important process involved in the regulation of energy expenditure. It can also explain part of the observed threefold range in cost of weight gain between individuals during overfeeding. However, to decipher what happens exactly upon cold exposure and overfeeding, more research is needed. Especially integrating data obtained from different organs (foremost muscle and brown adipose tissue) with whole body measures will give new and essential information. To investigate whether diminished adaptive thermogenesis causes obesity, or whether it is just a result of being overweight, longitudinal studies are necessary, following subjects over a longer period of time.
