“An immediate reaction to hunger is to secrete adrenalin, which...
Master Metabolism@lowmegatron
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May 19, 2025
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“An immediate reaction to hunger is to secrete adrenalin, which draws glucose from the liver and fats from the fatty tissues. When the liver’s glycogen is depleted, cortisol is produced to mobilize amino acids from muscles and other tissues, to provide energy.
Muscle protein is very rich in tryptophan and cysteine, and these amino acids suppress the thyroid gland’s function, and are potentially toxic to nerves, especially in the presence of cortisol and hypoglycemia. Tryptophan is turned into serotonin, which promotes lipid peroxidation, blood clotting, and certain patterns of nerve activity. Serotonin can suppress mitochondrial respiration, and along with the reduced body temperature that it produces, a pattern of torpor or helplessness tends to be produced.” Ray Peat
Muscle protein is very rich in tryptophan and cysteine, and these amino acids suppress the thyroid gland’s function, and are potentially toxic to nerves, especially in the presence of cortisol and hypoglycemia. Tryptophan is turned into serotonin, which promotes lipid peroxidation, blood clotting, and certain patterns of nerve activity. Serotonin can suppress mitochondrial respiration, and along with the reduced body temperature that it produces, a pattern of torpor or helplessness tends to be produced.” Ray Peat
Master Metabolism@lowmegatron
How Serotonin Makes You Fat, Cold, and Diabetic
► Serotonin decreases brain energy (ATP).
“Injection of serotonin to rats, induced a dramatic fall in brain ATP level... the activity of cytosolic phosphofructokinase, the rate-limiting enzyme of glycolysis, was significantly enhanced. Stimulation of anaerobic glycolysis was also reflected by a marked increase in lactate content in the brain.“ [1]
“Serotonin activates glycolysis, forming lactic acid. Excess lactic acid tends to decrease efficient energy production by interfering with mitochondrial respiration.“
Ray Peat
► Brain serotonin causes hypothermia, a sign of lower metabolic rate.
“The data suggest that an increase in serotonin levels in the brain decreases heat production and/or increases heat loss and leads to hypothermia in rats.” [2]
► Serotonin-deficient animals are resistant to obesity, insulin resistance, and nonalcoholic fatty liver disease,
► Serotonin reduces energy expenditure (“CO”).
“Recent findings suggest that increased peripheral serotonin and polymorphisms in TPH1 are associated with obesity; however, whether this is directly related to reduced BAT thermogenesis and obesity is not known.”
► TPH1 is an enzyme that creates serotonin in the brain.
► Genetic manipulation or the use of drugs to deplete serotonin via TPH1 induce resistance to metabolic destruction.
“We find that Tph1-deficient mice fed a high-fat diet are protected from obesity, insulin resistance and nonalcoholic fatty liver disease (NAFLD) while exhibiting greater energy expenditure by brown fat.”
“Small-molecule chemical inhibition of Tph1 in HFD-fed mice mimics the benefits ascribed to Tph1 genetic deletion, effects that depend on UCP1-mediated thermogenesis.”
► UCP1 is an enzyme that causes mitochondrial uncoupling, increasing the burn rate of “calories” by generating heat.
“As obesity increases peripheral serotonin, the inhibition of serotonin signaling or its synthesis in adipose tissue may be an effective treatment for obesity and its comorbidities.” [3]
[Tph1−/−are low serotonin mice]
► Serotonin decreases brain energy (ATP).
“Injection of serotonin to rats, induced a dramatic fall in brain ATP level... the activity of cytosolic phosphofructokinase, the rate-limiting enzyme of glycolysis, was significantly enhanced. Stimulation of anaerobic glycolysis was also reflected by a marked increase in lactate content in the brain.“ [1]
“Serotonin activates glycolysis, forming lactic acid. Excess lactic acid tends to decrease efficient energy production by interfering with mitochondrial respiration.“
Ray Peat
► Brain serotonin causes hypothermia, a sign of lower metabolic rate.
“The data suggest that an increase in serotonin levels in the brain decreases heat production and/or increases heat loss and leads to hypothermia in rats.” [2]
► Serotonin-deficient animals are resistant to obesity, insulin resistance, and nonalcoholic fatty liver disease,
► Serotonin reduces energy expenditure (“CO”).
“Recent findings suggest that increased peripheral serotonin and polymorphisms in TPH1 are associated with obesity; however, whether this is directly related to reduced BAT thermogenesis and obesity is not known.”
► TPH1 is an enzyme that creates serotonin in the brain.
► Genetic manipulation or the use of drugs to deplete serotonin via TPH1 induce resistance to metabolic destruction.
“We find that Tph1-deficient mice fed a high-fat diet are protected from obesity, insulin resistance and nonalcoholic fatty liver disease (NAFLD) while exhibiting greater energy expenditure by brown fat.”
“Small-molecule chemical inhibition of Tph1 in HFD-fed mice mimics the benefits ascribed to Tph1 genetic deletion, effects that depend on UCP1-mediated thermogenesis.”
► UCP1 is an enzyme that causes mitochondrial uncoupling, increasing the burn rate of “calories” by generating heat.
“As obesity increases peripheral serotonin, the inhibition of serotonin signaling or its synthesis in adipose tissue may be an effective treatment for obesity and its comorbidities.” [3]
[Tph1−/−are low serotonin mice]