Elsevier

Medical Hypotheses

Volume 74, Issue 3, March 2010, Pages 578-589
Medical Hypotheses

Metabolic syndrome: Aggression control mechanisms gone out of control

https://doi.org/10.1016/j.mehy.2009.09.014Get rights and content

Summary

An upcoming hypothesis about the evolutionary origins of metabolic syndrome is that of a ‘soldier’ to ‘diplomat’ transition in behaviour and the accompanying metabolic adaptations. Theoretical as well as empirical studies have shown that similar to the soldier and diplomat dichotomy, physically aggressive and non-aggressive strategists coexist in animal societies with negative frequency dependent selection. Although dominant individuals have a higher reproductive success obtained through means such as greater access to females, subordinate individuals have alternative means such as sneak-mating for gaining a substantial reproductive success. The alternative behavioural strategies are associated with different neurophysiologic and metabolic states. Subordinate individuals typically have low testosterone, high plasma cholesterol and glucocorticoids and elevated serotonin signalling whereas dominant ones are characterized by high testosterone, low brain serotonin and lower plasma cholesterol. Food and sex are the main natural causes of aggression. However, since aggression increases the risk of injury, aggression control is equally crucial. Therefore chronic satiety in the form of fat should induce aggression control. It is not surprising that the satiety hormone serotonin has a major role in aggression control. Further chronically elevated serotonin signalling in the hypothalamus induces peripheral insulin resistance. Meta-analysis shows that most of the anti-aggression signal molecules are pro-obesity and pro-insulin-resistance. Physical aggression is known to increase secretion of epidermal growth factor (EGF) in anticipation of injuries and EGF is important in pancreatic beta cell regeneration too. In anticipation of injuries aggression related hormones also facilitate angiogenesis and angiogenesis dysfunction is the root cause of a number of co-morbidities of insulin resistance syndrome. Reduced injury proneness typical of ‘diplomat’ life style would also reorient the immune system resulting into delayed wound healing on the one hand and increased systemic inflammation on the other. Diabetes is negatively associated with physically aggressive behaviour. We hypothesize that suppression of physical aggression is the major behavioural cue for the development of metabolic syndrome. Preliminary trials of behavioural intervention indicate that games and exercises involving physical aggression reduce systemic inflammation and improve glycemic control.

Introduction

The metabolic syndrome comprising insulin resistance, central obesity, type 2 diabetes, hypercholesterolemia, hypertension, atherosclerosis and coronary artery disease is considered a lifestyle disorder. However, the evolutionary origins of this syndrome are debated. The long standing hypotheses of thrifty gene [1] and thrifty phenotype [2] or epigenotype [3] have been challenged on several grounds and alternatives are suggested [4], [5], [6], [7], [8]. Some of the critics of thriftiness family of hypotheses have completely rejected the concept [4], [5], whereas others have pointed out the inadequacies of the hypotheses and suggested alternatives which are not incompatible with thriftiness hypotheses [6], [9]. One of the alternative hypotheses which says that the metabolic changes are adaptive to a ‘soldier’ to ‘diplomat’ transition in lifestyle appears to explain most of the metabolic, immunological, reproductive and cognitive changes known to accompany insulin resistance [6], [9]. Belsare [10] pointed out that this Watve–Yajnik hypothesis can account for thriftiness and that thriftiness can be a subset of the hypothesis. The hypothesis also accounts for fetal origins of metabolic disorders [6]. However, certain questions remain unanswered and some scepticism on the Watve–Yajnik hypothesis is possible. It can be argued that the ‘soldier’ and ‘diplomat’ are typical human traits of fairly recent cultural origin. Therefore whether there has been sufficient evolutionary time to evolve physiological switches for such responses is questionable. Secondly the molecular mechanisms that convert a soldier to diplomat transition into insulin resistance are also not well elucidated so far. In this paper we refine and reshape the Watve–Yajnik hypothesis and further argue that alternative behavioural strategies parallel to the ‘soldier to diplomat’ metaphor are commonly present in animal societies and that the neuro-endocrinological and metabolic changes accompanying these strategies can explain insulin resistance and accompanying disorders.

In a wide variety of species males compete for females and mating behaviour necessitates aggression and dominance. However males that are weak, submissive or subordinate are not complete reproductive failures. In a wide variety of species subordinate males remain with the harem submissively and sneak-mate opportunistically [11], [12], [13], [14]. Thus two alternative male mating strategies can coexist and be differentially successful. Game theory has shown that aggressive and submissive, i.e. ‘hawk’ and ‘dove’ strategies can coexist at a stable equilibrium in a population [15]. Selection for ‘hawk’ or ‘dove’ strategies is negatively frequency dependent, i.e. in a population predominated by doves, hawks have a greater fitness advantage and vice versa. There is some evidence that even in human societies the contribution of physical aggression to reproductive success is negatively frequency dependent. The reproductive success of aggressive individuals was greater than submissive ones in the Yanomamo societies but was lower in the Waorani tribe where the frequency of aggressive encounters was much higher [16]. A more complex example of coexistence of alternative strategies is that of lizard males with small territories, those with large territories and those without territories that coexist in a rock–paper–scissor like game [17]. These empirical studies and theoretical models imply that negative frequency dependent selection on two or more alternative ways of gaining success can lead to genetic polymorphism in a population. This is important because one major criticism of the thrifty gene hypothesis can be that the presumed selective advantages of thriftiness would result in directional selection making every individual ‘thrifty’ and polymorphism is an unlikely outcome, whereas selection for soldier–diplomat or hawk–dove strategies can theoretically lead to a stable polymorphism.

Alternative strategies work not only for mate competition but also apply to food access, stress response and other factors. For example while stronger and dominant individuals fight for a patch of food, the submissive ones may wait and watch for opportunities to sneak. Two distinct classes of coping strategies are demonstrated in rodents in which the aggressive strategists show an active response to stress situations and in situations of defeat they react with flight or escape. On the other hand the non-aggressive strategists are passive and in aversive situations react by immobility and withdrawal rather than flight and escape [18]. The ‘hawk–dove’ dichotomy in animals has many parallels as well as some important differences with the ‘soldier–diplomat’ dichotomy in humans. Both ‘doves’ and ‘diplomats’ avoid physical confrontation. Both need to be socially smart and opportunistic and thereby compensate for physical subordination. However there are two important differences between ‘doves’ and ‘diplomats’:

  • (i)

    In animal societies subordinate individuals generally have a lower social status. Patches of richer food are more likely to be snatched by dominant individuals leaving the subordinate ones with less calorie rich food. Since subordinate individuals are likely to have less as well as insecure access to food, they need to develop a “thrifty” metabolism and indulge in binge eating. Social subordination is shown to induce high fat intake and weight gain in animals [19] and this would be adaptive for individuals who have only occasional access to rich food. Unlike ‘doves’ in animal societies, ‘diplomats’ in modern human societies can have higher social status and continued access to calorie rich food. The high calorie availability for physically weak and inactive individuals poses a paradox that is characteristically human and more typical of modern lifestyle.

  • (ii)

    Physical aggression is the only predominant form of aggression in animals whereas verbal and political aggressions are alternative forms of aggression in humans. The metabolic requirements of the different forms of human aggression are likely to be much different. In our hypothesis below we use the term aggression to imply predominantly physical aggression. Verbal and political aggressions are assumed to be components of ‘diplomat’ rather than ‘soldier’ strategy.

Despite the two important differences, the close parallels between animals and humans in the behavioural dichotomy imply that metabolic adaptations accompanying behavioural shifts speculated by the Watve–Yajnik hypothesis could have arisen very early in evolution.

A number of studies have shown that diabetic rats show loss of aggression and increased submissive displays (review [20]) fitting well with the soldier–diplomat paradigm. It is difficult to infer from human data unless we clearly distinguish between physical and verbal aggression and not all studies make a clear distinction. However, a number of observations are compatible with animal experiments. Social subordination or low decision-latitude is shown to increase the risk for type 2 diabetes [21], low cholesterol levels are associated with aggression [22], [23], aggression suppression increases the risk of hypertension [24], [25], [26] and people negatively associate physical aggression with abdominal and overall obesity in a ‘body reading’ test [27]. Of particular interest is the record that incidence of diabetes was reduced during World Wars I, II [28], [29] and other long drawn wars such as the Sarajevan war [30]. In Sarajevo, during war time the percentage of hypertensive adults decreased and a large proportion of type 2 diabetic patients showed improved glycemic control without any medication [30]. All these studies attribute the improved epidemiological picture to dietary changes during war, but no data on dietary changes are given in support. It is equally likely that the war induced ‘soldier’ attitude could have played a role. These indications necessitate that the relationship of physical aggression and dominance with insulin resistance syndrome be examined carefully.

Section snippets

Hypothesis

We hypothesize that loss of physical aggression, which accompanies the ‘soldier’ to ‘diplomat’ transition, is central to the development of type 2 diabetes and other components of the metabolic syndrome. The molecular machinery of aggression control induces insulin resistance and insulin resistance helps shifting the energy budget allocation from muscles to brain to support a physically submissive but socially smart lifestyle. In addition aggression suppression is accompanied by disinvestment

The meta-analysis approach

If metabolic syndrome is primarily related to aggression control, the signalling molecules associated with aggression control could also be involved in inducing insulin resistance and associated physiological changes. We searched literature for all known endocrine mechanisms contributing to physical aggression or its control. Then we searched for the association of these mechanisms with any components of IRS. A wide variety of molecules were found to be associated with both aggression

Role of funding source

CSIR supported PB during the study period, partial funding was obtained from the University of Pune, KanBiosys and LabIndia for the volunteer trials.

Conflicts of Interest Statement

None declared.

Acknowledgements

We thank Charushila Kumbhar, Vinay Kolte, Pramod Patil and Archana Watve for their help in the volunteer trials, and all the volunteers of the study. We also thank Rajendra Deolankar and Pranay Goel for their comments on the manuscript.

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