What is thermogen's role in nonshivering thermogenesis?

Thermogenesis in Nonshivering Thermogenesis

Nonshivering thermogenesis (NST) is primarily mediated by brown adipose tissue (BAT) through uncoupling protein 1 (UCP1), which is the only mechanism capable of adaptive nonshivering thermogenesis in response to cold exposure. 1

Primary Mechanism: Brown Adipose Tissue

Brown adipose tissue is the sole tissue responsible for classical adaptive nonshivering thermogenesis, which is both facultative (activated acutely when extra heat is needed) and adaptive (capacity increases over weeks with sustained cold exposure). 2

• UCP1 is the exclusive mediator of adaptive NST in mammals, as demonstrated by studies showing that UCP1-ablated mice cannot recruit any alternative NST mechanisms even when exposed to extreme cold (4°C) requiring heat production at four times resting levels. 1

• BAT thermogenesis is controlled by sympathetic nervous system activity, which stimulates this tissue in response to cold exposure. 3

• The capacity for NST increases or decreases according to BAT growth or regression, which occurs based on the extent of cold or dietary stimulation. 3

Energy Expenditure Impact

• At standard housing temperatures (20-22°C), mice experience ~30% higher energy expenditure than basal metabolic rate due to enhanced NST by brown and beige fat, along with shivering thermogenesis by skeletal muscle. 4

• Housing at thermoneutral temperatures (28-32°C for mice) reduces the contribution of NST, though chronic thermoneutral acclimation impairs brown and beige fat biogenesis. 4

Alternative Mechanisms: Limited Role

While skeletal muscle NST has been proposed as an alternative mechanism, no UCP1-independent adaptive NST has been demonstrated in muscle or any other organ, even under prolonged enhanced demand for heat production. 1

• Muscle NST may be adaptive but not facultative, unlike UCP1-dependent NST, and reflects slow regulation with low energy efficiency. 5

• Shivering thermogenesis in skeletal muscle remains the primary non-BAT mechanism for heat production but is not classified as NST. 6

Clinical Relevance in Humans

• In cold-exposed humans, BAT activation contributes to total thermogenic rate, particularly in young lean adults, though the quantitative contribution relative to shivering requires further clarification. 6

• Cold acclimation and compounds that stimulate BAT thermogenesis may enhance cold endurance and potentially influence energy balance. 6

Important Caveats

Norepinephrine-induced increases in metabolism do not exclusively represent NST capacity—in non-adapted mammals, this response mainly reflects activity in organs not involved in NST; only the increase after cold adaptation represents true NST. 2

• Diet-induced thermogenesis is also likely mediated by BAT activity and shares the facultative and adaptive characteristics of cold-induced NST. 2, 3

• The ventromedial hypothalamus participates in controlling diet-induced thermogenesis in BAT but is not required for cold-induced NST. 3