Regulation of Energy Intake & Body Weight Regulation Flashcards
The body has elaborate mechanisms regulating food intake and energy balance.
a. Animals, including humans, tend to maintain a relatively constant body weight over extended periods of time.
i. Thus, like body temperature, there appear to be endogenous mechanisms maintaining a ‘set point’ for body weight.
b. However, unlike the set point for body temperature, the set point for body weight varies considerably from individual to individual and may change within an individual.
c. Nevertheless, the mechanisms regulating food intake and energy expenditure appear to operate to defend each individual’s current “set point”.
d. Experimentally this feature can be seen when animals are either food restricted or force-fed for a period of time to reduce or increase body weight
i. Once the stimulus is terminated, the animal’s weight returns to control values.
Animal and Set point
a. Animals tend to adjust their food intake to achieve a normal body weight.
b. The graph shows a schematized growth curve for 3 groups of rats that were either (a) force-fed, (b) allowed free access to food, or (c) food restricted for the period between the arrows.
c. Note that the animals slowly returned to “normal” weight when allowed free access to food
Short- and Long-term physiologic/ homeostatic regulators
a. In understanding the control of body weight. there are both short- and long-term physiologic/ homeostatic regulators
i. for each regulator a variety of neural and blood-borne factors determine whether feeding will be prompted or inhibited.
b. A signal that produces satiety after a single meal is very different from a signal that provides long-term regulation of body weight.
i. The former (satiety) controls meal size and short-term fuel availability; the latter is a determinant of adiposity.
d. In addition, non-physiologic or non-homeostatic signals are extremely important in the regulation of energy balance.
i. This is especially true in humans.
e. These include reward and motivational mechanisms, learned behaviors, emotions, social context, and environmental cues to name a few. Furthermore, there are likely important interactions between homeostatic and non-homeostatic signals
The hypothalamus is intimately involved in both the control of short- and long-term regulation of body weight.
The paraventricular nucleus (PVN), ventromedial nucleus (VMN), arcuate nucleus (Arc), and lateral hypothalamus (LH) regulate food intake and disposition by processing information concerning peripheral energy stores and then stimulating or inhibiting feeding or altering gastric motility and food metabolism/utilization.
What four ares of the brain… regulate food intake and disposition by processing information concerning peripheral energy stores and then stimulating or inhibiting feeding or altering gastric motility and food metabolism/utilization.
The paraventricular nucleus (PVN), ventromedial nucleus (VMN), arcuate nucleus (Arc), and lateral hypothalamus (LH)
Short-Term Regulation of Food Intake
a. Short term regulation of food intake involves cues to initiate feeding (hunger) and cues to stop feeding (satiety).
b. Thus, these are the signals involved in potentially determining meal size and frequency.
c. Early studies identified the lateral hypothalamus as the ‘hunger center’ and the ventromedial nucleus as the ‘satiety center’.
The Lateral Hypothalamus (LH)
a. Stimulation of the lateral hypothalamus (LH) produces voracious eating, even in a food replete animal, and lesions in this region produced aphagia (no eating).
b. Two peptides have been identified that are expressed in the brain only by neurons in the LH: melanin concentrating hormone (MCH) and orexins (also known as hypocretins).
c. These peptides induce feeding when injected into the CNS. The MCH and orexin neurons in the LH have very similar projection patterns, including the brainstem motor systems that support behaviors like chewing, licking, and swallowing.
d. These include cranial nerve motor neurons in the trigeminal, facial, and hypoglossal motor nuclei, as well as the reticular areas that surround them and which constitute pattern generators for these behaviors.
e. The MCH and orexin neurons also innervate sympathetic and parasympathetic preganglionic nuclei in the medulla and the spinal cord.
What doe stimulation of the lateral hypothalamus cause? What about a lesion to the lateral hypothalamus
Stimulation of the lateral hypothalamus (LH) produces voracious eating, even in a food replete animal,
Lesions in this region produced aphagia (no eating).
Two peptides have been identified that are expressed in the brain only by neurons in the Lateral Hypothalamus
*Important slide
Melanin Concentrating Hormone (MCH) and Orexins (also known as hypocretins).
a. These peptides induce feeding when injected into the CNS.
b. The MCH and orexin neurons in the LH have very similar projection patterns, including the brainstem motor systems that support behaviors like chewing, licking, and swallowing.
i. These include cranial nerve motor neurons in the trigeminal, facial, and hypoglossal motor nuclei, as well as the reticular areas that surround them and which constitute pattern generators for these behaviors.
c. The MCH and orexin neurons also innervate sympathetic and parasympathetic preganglionic nuclei in the medulla and the spinal cord.
Ventromedial Nucleus (VMN)
a. Opposite effects are seen in the ventromedial nucleus (VMN) compared to the lateral hypothalamus
b. Evidence that the VMN acts as a ‘satiety’ center comes from the observation that stimulation of this region results in cessation of eating even in hungry animals.
c. Animals with lesions in this region eat excessively and become obese.
i. Lesioned animals may reach 3-4 times normal weight within several months.
ii. Once this weight is reached, the animals reduce their food intake to simply maintain their increased weight.
iii. If they are force-fed to further increase their weight, they subsequently reduce their eating to lose weight back to the post-lesion level. If they are food-restricted, they subsequently eat to regain the weight.
d. Thus, VMN lesions have the effect of “resetting” the regulated weight to a higher level.
What does the Ventromedial Nucleus do?
a. Evidence that the VMN acts as a ‘satiety’ center comes from the observation that stimulation of this region results in cessation of eating even in hungry animals.
i. stimulation of VMN= stops eating, lowers weight
b. Animals with lesions in this region eat excessively and become obese.
i. Lesioned animals may reach 3-4 times normal weight within several months.
ii. Once this weight is reached, the animals reduce their food intake to simply maintain their increased weight.
Although the VMN and LH were the first hypothalamic regions recognized for their role in regulating appetite and satiety, the Arcuate and Paraventricular nuclei are also extremely important.
Large Summary
a. The arcuate nucleus contains “first order” neurons that promote either food intake or satiety.
b. Activation of arcuate neurons that produce both neuropeptide Y (NPY) and agouti-related peptide (AgRP) promote feeding while activation of the arcuate neurons that produce both α-melanocyte stimulating hormone (α-MSH) and cocaine and amphetamine-related transcript (CART) promote satiety.
c. Remember, α-MSH is a product of the proopiomelanocortin (POMC) precursor molecule.
i. These two neuron populations innervate many of the same targets in the hypothalamus including the paraventricular nuclei (PVN) and LH.
ii. . In addition, the α-MSH/CART neurons directly innervate sympathetic preganglionic neurons in the spinal cord.
d. α-MSH activates melanocortin receptors (MCR) while AgRP blocks the effect of α-MSH at these receptors.
i. MCRs are expressed in PVN and LH as well as by preganglionic sympathetic and parasympathetic neurons in the medulla and spinal cord.
e. Activation of MCRs induces satiety.
i. NPY increases hunger when injected into the hypothalamus and decreases energy expenditure (via inhibition of the sympathetic nervous system and perhaps by inhibition of thyroxin and growth hormone secretion).
f. Thus, the NPY/AgRP neurons are thought to constitute a potent feeding system that is actively opposed by the α-MSH/CART satiety system.
i. These neurons express receptors for peripherally generated hormones (see below) that participate in regulation of food intake, and these hormones can alter the balance between these opposing systems.
Arcuate Neuron and what it creates
Arcuate Neuron’s products:
- Feeding molecules: both Neuropeptide Y (NPY) and agouti-related peptide (AgRP) promote feeding
i. NPY increases hunger when injected into the hypothalamus and decreases energy expenditure (via inhibition of the sympathetic nervous system and perhaps by inhibition of thyroxin and growth hormone secretion)
ii. AgRP blocks the effect of α-MSH at these receptors - Satiety Molecules: α-melanocyte stimulating hormone (α-MSH) and cocaine and amphetamine-related transcript (CART)
i. the α-MSH/CART neurons directly innervate sympathetic preganglionic neurons in the spinal cord
ii. α-MSH activates melanocortin receptors (MCR), Activation of MCRs induces satiety
*MCRs are expressed in PVN and LH as well as by preganglionic sympathetic and parasympathetic neurons in the medulla and spinal cord. Activation of MCRs induces satiety
What are the feeding molecules that the Arcuate Nucleus creates?
Feeding molecules: both Neuropeptide Y (NPY) and agouti-related peptide (AgRP) promote feeding
a. NPY increases hunger when injected into the hypothalamus and decreases energy expenditure (via inhibition of the sympathetic nervous system and perhaps by inhibition of thyroxin and growth hormone secretion).
b. Thus, the NPY/AgRP neurons are thought to constitute a potent feeding system that is actively opposed by the α-MSH/CART satiety system.
What are the Satiety molecules that the Arcuate Nucleus creates?
Satiety Molecules: α-melanocyte stimulating hormone (α-MSH) and cocaine and amphetamine-related transcript (CART)
a. The α-MSH/CART neurons directly innervate sympathetic preganglionic neurons in the spinal cord
b . α-MSH activates melanocortin receptors (MCR), Activation of MCRs induces satiety
-AgRP blocks the effect of α-MSH at these receptors
c. MCRs are expressed in PVN and LH as well as by preganglionic sympathetic and parasympathetic neurons in the medulla and spinal cord. Activation of MCRs induces satiety.
