Myth of Hypothalamic Hunger and Satiety Centers

Myth of Hypothalamic Hunger and Satiety Centers

  • (Dual centre hypothesis) Eating behavior is controlled by two different regions of the hypothalamus
    • Satiety Centre: Ventromedial hypothalamus (VMH)
    • Feeding / Hunger Centre: Lateral hypothalamus (LH)

 

VMH Satiety Center

  • 1940 (Hetherington & Ranson): Large bilateral electrolytic lesions to the ventromedial hypothalamus produce hyperphagia (excessive eating) and extreme obesity in rats
  • Two different phases of the VMH syndrome
    • Dynamic phase
      • Begins as soon as the subject regains consciousness after the operation
      • Several weeks of grossly excessive eating and rapid weight gain
      • Consumption gradually declines to a level that is just sufficient to maintain a stable level of obesity (beginning of the static phase)
    • Static phase
      • Consumption gradually declines to a level that is just sufficient to maintain a stable level of obesity (beginning of the static phase)
      • Animal maintains its new body weight
        • If a rat in the static phase is deprived of food until it has lost its substantial amount of weight, it will regain the lost weight once deprivation ends
        • If it is made to gain weight by forced feeding, it will lose the excessive weight once the forced feeding is curtailed
      • VMH-lesioned rats seem less hungry than unlesioned controls
        • VMH-lesioned rats eat much more than normal rats when palatable food is readily available
        • Less willing to work for it (Teitelbaum, 1957) or to consume it if it is slightly unpalatable (Miller, Bailey, & Stevenson, 1950)
      • Finicky eating of VMH-lesioned rats is a consequence of their obesity, not a primary effect of their lesion (Weingarten, Chang, and Jarvie)
        • No less likely to consume unpalatable food than are unlesioned rats of equal obesity

 

LH Feeding Center

  • 1951 (Anand & Brobeck): Bilateral electrolytic lesions to the lateral hypothalamus produce aphagia
    • Aphagia: a complete cessation of eating
    • Rats that were first made hyperphagic by VMH lesions were rendered aphagic by the addition of LH lesions
    • Lateral region of the hypothalamus is a feeding center
  • Aphagia is accompanied by adipsia
    • Adipsia: a complete cessation of drinking
    • LH-lesioned rats partially recover if they are kept alive by tube feeding
      • At first, the rats eat wet, palatable foods, such as chocolate chip cookies soaked in milk
      • Eventually, they will eat dry food pellets if water is concurrently available

 

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Glucostatic Theory

 

Reinterpretation of the Effects of VMH and LH Lesions

  • VMH: Satiety center crumbled in the face of two lines of evidence
    • First, the primary role of the hypothalamus is the regulation of energy metabolism, not the regulation of eating
      • VMH-lesioned animals become obese because they overeat vs. they overeat because they become obese
      • Bilateral VMH lesions increase blood insulin levels, which increases lipogenesis and decreases lipolysis
        • Lipogenesis: production of body fat
        • Lipolysis: breaking down of body fat to utilizable forms of energy
        • Both are likely to be the result of the increases in insulin levels, that occur following the lesion
        • Because the calories ingested by VMH-lesioned rats are converted to fat at a high rate, the rats must keep eating to meet their energy requirement
      • Second level of evidence showed that many of the effects of VMH lesions are not attributable to VMH damage
        • Two areas that have been investigated: arcuate nuclei and paraventricular nuclei
          • Arcuate nuclei: Regulates feeding behavior
            • Agouti-related protein (AgRP), which are neurotransmitters released by neuropeptide neurons located in the arcuate nucleus, strongly stimulate food intake
            • Other neuron groups produce two substances that can cause an appetite suppressing reponse – cocaine and ampethamine regulated transcript (CART) and pro-opiomelanocortin (POMC)
            • Gut peptides, which signals to the hypothalamus via the arcuate nuclei, also provide appetite modifying neurotransmitters such as the opioid peptides and alpha-melanocyte stimulating hormone ( -MSH)
          • Paraventricular nuclei (PVN): A large fiber bundle, the ventral noradrenergic bundle, courses past the VMH and is thus inevitably damaged by large electrolytic VMH lesions –particularly fibers that project from the nearby PVN
            • PVN contains nerve cells which release corticotrophin releasing hormone that projects to the arcuate nucleus and locus coeruleus
          • Stimulation of the PVN produces hyperphagia and obesity, just as VMH lesions do
            • Microinjections of noradrenaline into the PVN increases carbohydrate consumption
            • NPY stimulation to the PVN triggers increase in daily intake of carbohydrates and fat resulting in dramatic weight gain in female rats
          • LH is a feeding center (early research – focused on aphagia and adipsia) vs. LH lesions produce a wide range of severe motor disturbances and a general lack of responsiveness to sensory input (subsequent research) à LH is a center specifically dedicated to feeding

 

 

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