Circadian rhythms and clocks in adipose tissues: current insights

Figures & data

Figure 1 Different zeitgebers reset the circadian clock network. The circadian master pacemaker in the SCN receives light information via ipRGCs to coordinate peripheral and central subordinate clocks. In this way, behavior and physiological processes are aligned to time-of-day-specific requirements. Peripheral tissue clocks are sensitive to food-mediated signals and adjust to alterations in the diurnal feeding regime. Because food resetting does not affect the SCN, mistimed feeding promotes internal desynchrony.

Abbreviations: ARC, arcuate nucleus; SCN, suprachiasmatic nucleus; ipRGCs, intrinsically photosensitive retinal ganglion cells; CNS, central nervous system.

Figure 2 Adipocyte clocks and adipose physiological rhythms. The expression patterns of several adipose genes are under circadian control regulating adipose over the course of the day.

Abbreviations: TGFβ, transforming growth factor beta; CCL2, C-C motif chemokine ligand; SREBF, sterol regulatory element-binding transcription factor; FABP4, fatty acid-binding protein 4; C/EBP, CCAAT-enhancer-binding protein; IL-10, interleukin-10; TNFα, tumor necrosis factor alpha; PPARs, peroxisome proliferator-activated receptors; HSL, hormone-sensitive lipase.

Table 1 Overview of adipose tissue phenotypes of clock gene-mutant mice

Clock genes	Body weight	Adipose tissue	Food intake	Blood lipids	Adipokines	References
Bmall	↑/↓ on NC (age effect) ↔/↑ on HFD	↑ adiposity on NC and HFD	↔ on NC and HFD	↑ TGs (n.r.) ↑ cholesterol and NEFAs on HFD ↓ FAAs and glycerol (n.r.)	↑ leptin, adiponectin, PAI-1	7,35,40,62,63,65,109
Clock (C57BL/6)	↑ on NC & HFD	↑ adiposity	↑ on NC and HFD dampened rhythm	↑ TGs and cholesterol ↓ FFAs and glycerol (n.r.)	↑ leptin	38,42
Clock (CBA)	↔ on NC ↓ on HFD	↔ adiposity		↓ FFAs on NC and HFD	↑ adiponectin on NC ↔ leptin on NC ↔ adiponectin on HFD ↓ leptin on HFD	59,60
Clock (ICR)	↔ on NC		↔ on NC and	↔/↓ TGs and FFAs on	↔ leptin on NC and	61
	↔/↓ on HFD		HFD	NC ↔ TGs on HFD ↑ FFAs on HFD	HFD
Cryl/2	↓ on NC and HFD	↓ adiposity on NC ↑ adiposity on HFD	↔ on NC ↓ on HFD dampened rhythm	↔ TGs, cholesterol and FFAs on HFD	↓ leptin on NC ↔ leptin on HFD	40,68,69
Perl	↓ on NC		↑ on NC (relative to body weight)			70
Per2	↑ on NC ↑ on HFD	↑ adiposity on HFD	↔/↑ on NC ↑ on HFD dampened rhythm			70,72
Per3	↔ on NC ↑ on HFD	↑ adiposity on NC and HFD	↔ on chow and HFD			73
Perl/2	↑ on NC	↑ adiposity	↔ on chow dampened rhythm		↑ leptin (n.r.)	74
Perl–3	↑ on HFD	↑ adiposity on HFD	↑ on chow (rel. to BW) and HFD			72
RevErbα	↔/↑ on NC ↑ on HFD	↑ adiposity on NC and HFD	↔ on chow	↓ TGs and glycerol on HFD ↑ LDL, cholesterol and NEFAs on HFD	↑ leptin & adiponectin on NC & HFD	72,73
RORα	↓ on NC and HFD	↓ adiposity on NC and HFD	↑ on HFD	↓ cholesterol, HDL, and NEFAs ↓ FFAs on HFD	↓ leptin mRNA in wAT	32,76

Note: Arrows indicate increased (↑), unaltered (↔), and decreased (↓) levels compared to controls.

Abbreviations: n.r, not rhythmic; NC, normal chow; HFD, high-fat diet; FFA, free fatty acid; NEFA, non-esterified fatty acid; TG, triglyceride; BW, body weight; L/HDL, low-/high-density lipoprotein.

Figure 3 Adipose–brain cross talk in the regulation of energy homeostasis. Rhythmically regulated adipokines cross the blood–brain barrier to affect appetite- and energy expenditure-regulating circuits in the mediobasal hypothalamus (MBH). In turn, altered energy intake and demands remodulate adipose function along the day.

Abbreviations: POMC, pro-opiomelanocortin; NPY, neuropeptide Y; IL-6, interleukin 6; TNFa, tumor necrosis factor alpha.