The Circadian Regulation of Nutrient Metabolism in Diet-Induced Obesity and Metabolic Disease

Abstract

Obesity and other metabolic diseases are major public health issues that are particularly prevalent in industrialized societies where circadian rhythmicity is disturbed by shift work, jet lag, and/or social obligations. In mammals, daylight entrains the hypothalamic suprachiasmatic nucleus (SCN) to a ≈24 h cycle by initiating a transcription/translation feedback loop (TTFL) of molecular clock genes. The downstream impacts of the TTFL on clock-controlled genes allow the SCN to set the rhythm for the majority of physiological, metabolic, and behavioral processes. The TTFL, however, is ubiquitous and oscillates in tissues throughout the body. Tissues outside of the SCN are entrained to other signals, such as fed/fasting state, rather than light input. This system requires a considerable amount of biological flexibility as it functions to maintain homeostasis across varying conditions contained within a 24 h day. In the face of either circadian disruption (e.g., jet lag and shift work) or an obesity-induced decrease in metabolic flexibility, this finely tuned mechanism breaks down. Indeed, both human and rodent studies have found that obesity and metabolic disease develop when endogenous circadian pacing is at odds with the external cues. In the following review, we will delve into what is known on the circadian rhythmicity of nutrient metabolism and discuss obesity as a circadian disease.

PPARG stimulation restored lung mRNA expression of core clock, inflammation‐ and metabolism‐related genes disrupted by reversed feeding in male mice

“…These data showed that RF reprogrammed the peripheral lung clock. Our observation correlated with other references that the time of food consumption was a powerful factor affecting the circadian rhythm in metabolically active organs and tissues (Bilu et al, 2022 ; Glad et al, 2011 ; Kim et al, 2023 ; Pickel & Sung, 2020 ; Woodie et al, 2022 ). For lung circadian molecular clock gene expression, such influence was described for tobacco smoking (Choukrallah et al, 2020 ; Khan et al, 2019 ; Numaguchi et al, 2016 ).…”

Hepatic Vagal Afferents Convey Clock-Dependent Signals to Regulate Circadian Food Intake

“…This lends credence to and provides mechanistic insights into previous findings that HVAN blockade reduces body weight gain on HFD ( 34 , 35 ). Our findings have broad reaching implications for the obesity epidemic since healthy circadian rhythms are disrupted by poor diet and obesity ( 10 ). Consuming the majority of calories late in the day and/or night eating syndrome are correlated with obesity, poor metabolic outcomes and non-alcoholic fatty liver disease in human patients ( 36–38 ).…”

“…Synchrony between the light-entrained SCN and food-entrained liver is critical for maintaining chrono-metabolic homeostasis in the face of varying environmental cues ( 6 – 9 ). Rodent and human studies have shown that desynchrony between these tissues is detrimental to organismal health ( 6 , 7 , 10 ). Although the consequences of circadian desynchrony are well known, the mechanism through which synchrony and desynchrony are communicated within an organism remains a major unanswered question.…”

Sleep–wake changes and incident depressive symptoms in midlife women

“…Sleep–wake changes has been implicated in the progression of metabolic diseases 1 , 2 , cardiovascular diseases 3 , 4 , neurodegeneration 5 , 6 , and psychiatric disorders 7 – 9 . Therefore, for individuals, maintaining a certain level of sleep–wake rhythm homeostasis is essential for wellness, especially for mental health.…”