Hypothalamus Lesions and Unexplained Weight Gain: Can "Excess Calories" Really Cause This Weight Gain?

Lesions to the hypothalamus and other injuries to the brain have been clinically shown to lead to weight changes in some patients. What's going on inside these patients? And what might these phenomena tell us about the root of the obesity epidemic?

Many researchers believe that the hypothalamus/pituitary region of the brain plays a key role in appetite regulation. When injuries occur to that part of the brain, they note, patients often become ravenously hungry and gain weight. The Caloric Balance Hypothesis tells us that brain injuries cause hunger. Hunger drives patients to consume superfluous calories. Thus, a positive caloric balance causes the increase in body fat.

The Lipophilia Hypothesis argues that obesity is a physiological phenomenon caused by hormonal disregulation of adipose tissue. Changes in eating behavior and in calorie expenditure are consequential not causal. Brain injuries cause changes to insulin levels, thus changing the constitution of the fat tissue itself - making it bigger. The increased adipose tissue needs more calories to "maintain its stock" and thus drives the hunger and, ultimately, the positive caloric balance.

1. Gary Taubes discusses how researchers came believe that hypothalamus induced obesity supports the Caloric Balance Hypothesis, even though the evidence strongly argues for the Lipophilia Hypothesis. You can review this discussion – it's lengthy and technical but thoroughly convincing – on pages 366-375 of Good Calories Bad Calories.[1] In particular, Taubes discusses a theoretical debate between two researchers -- John Brubeck and Steven Ranson -- about the origins of brain injury induced obesity. Brubeck argued for what is essentially a caloric balance perspective – suggesting that brain damage leads to hyperphagia (i.e. "overeating") and that this overeating accounts for the obesity seen in patients. But this hypothesis fails to account for all the evidence.

As Taubes notes, Ranson suggested that injuries to a region of the brain called the ventromedial hypothalamus ultimately drive nutrients out of organ and muscle tissues and into fat tissue. This creates a strange condition dubbed "internal starvation." This fundamental starvation leads to the hunger associated with brain damage. As long as the fat tissues continue to rob the muscle and organ tissues of nutrients, hunger will persist. Deny calories to these hungry people/animals, and the body will respond by literally shutting down its metabolism to conserve energy.

The evidence for this idea – both in humans and in animals – seems remarkably compelling.

Randomly selected internet articles on brain injury and weight gain also confirm that disregulation of energy homeostasis most likely has a physiological basis.

2. Consider this article from the journal of Neurotrauma: "Mitochondrial dysfunction and calcium perturbation induced by traumatic brain injury."[2]

The authors discuss traumatic brain injury (TBI) in rats. They found that TBI actually changes the rate at which mitochondria in cells respirate.

3. Consider this article on TBI, as well: "Assessment of neuroendocrine dysfunction following traumatic brain injury."[3]

The authors describe how traumatic brain injury -- in two different cases -- led to "metabolic abnormalities [such as] depressed cortisol and thyroid function."

4. Here is another interesting article: "Outcomes from pediatric traumatic brain injury."[4]

The authors conclude that:"hyperglycemia and poor neurologic outcome in head injured children are associated."

They also tell us that "an ambiguous association exists in adult patients between hyperglycemia, severity of head injury, and outcome of traumatic head injury."

So why would hyperglycemia – an overabundance of sugar in the blood – associate with head injury if calories alone determine how fat we get?

5. Here is another article: "Endocrine abnormalities in severe traumatic brain injury – a cue to prognosis and severe craniocerebral trauma?"[5]

The authors write: "patients with severe cranial and cerebral trauma display metabolic and endocrine changes."

They also tells us that some TBI patients have "elevated insulin."

You can look practically anywhere and find evidence that the hypothalamus/pituitary region regulates many homeostatic functions in the body. So if and when a disturbance in this region associates with changes in weight, your first thought should not be "how might this change appetite?" but rather "how might this change the complex web of homeostasis in the body?"

The null hypothesis should be Lipophilia. Caloric Balance is a very odd and unconvincing way to look at this problem of hypothalamus induced weight gain.

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1. Taubes, Gary. "Good Calories, Bad Calories." pp 366-375. New York: Knopf (2007).

2. Y Xiong, Q Gu, PL Peterson, JP Muizelaar, CP Lee. "Mitochondrial dysfunction and calcium perturbation induced by traumatic brain injury." J Neurotrauma (1997) 14: 23-34.

3. CHILDERS M. K.; RUPRIGHT J.; JONES P. S.; MERVEILLE O. "Assessment of neuroendocrine dysfunction following traumatic brain injury." Brain injury1998, vol. 12, no6, pp. 517-523 (25 ref.)

4. COCHRAN Amalia; SCAIFE Eric R; HANSEN Kristine W.; DOWNEY Earl C. "Outcomes from pediatric traumatic brain injury." The Journal of trauma, injury, infection, and critical care 2003, vol. 55, no6, pp. 1035-1038.

5. Hackl JM, Gottardis M, Wieser C, Rumpl E, Stadler C, Schwarz S, Monkayo R. "Endocrine abnormalities in severe traumatic brain injury – a cue to prognosis and severe craniocerebral trauma?" Intensive Care Med. 1991;17(1):25-9.

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