Rudolf Schoenheimer and the Concept of the Dynamic State of Body Constituents

Guggenheim, K.

doi:10.1093/jn/121.11.1701

Cited by 25 publications

(18 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tissue-specific changes in glycerol and non-esterified fatty acids (NEFA) reflect continuous turnover and transport of lipids among tissues in a state of so-called “dynamic equilibrium” (Guggenheim, 1991), in which total body fat content remains constant in the midst of high rates of degradation, inter-conversion and re-esterification of lipid stores within and across tissues over 24-h. Interestingly, HFD blunted oscillation of circulating NEFAs, increased levels of serum glycerol, and severely reduced NEFA levels and oscillation in WAT and BAT (Figure 7A), suggesting an impaired diurnal turnover of lipid stores in both fat depots. In contrast, liver glycerol and NEFAs were dramatically increased on HFD, similar to skeletal muscle, highlighting known pathological deposition of biologically active lipids associated with obesity and insulin resistance.…”

Section: Resultsmentioning

confidence: 99%

Atlas of Circadian Metabolism Reveals System-wide Coordination and Communication between Clocks

Dyar

Lutter

Artati

et al. 2018

Cell

289

233

View full text Add to dashboard Cite

Metabolic diseases are often characterized by circadian misalignment in different tissues, yet how altered coordination and communication among tissue clocks relate to specific pathogenic mechanisms remains largely unknown. Applying an integrated systems biology approach, we performed 24-hr metabolomics profiling of eight mouse tissues simultaneously. We present a temporal and spatial atlas of circadian metabolism in the context of systemic energy balance and under chronic nutrient stress (high-fat diet [HFD]). Comparative analysis reveals how the repertoires of tissue metabolism are linked and gated to specific temporal windows and how this highly specialized communication and coherence among tissue clocks is rewired by nutrient challenge. Overall, we illustrate how dynamic metabolic relationships can be reconstructed across time and space and how integration of circadian metabolomics data from multiple tissues can improve our understanding of health and disease.

show abstract

Section: Resultsmentioning

confidence: 99%

Atlas of Circadian Metabolism Reveals System-wide Coordination and Communication between Clocks

Dyar

Lutter

Artati

et al. 2018

Cell

289

233

View full text Add to dashboard Cite

show abstract

“…This non-oxidative damage may be increased by the heat generated as a side effect of metabolism in the human body. Proteins are continuously broken down and re-synthesized through transcription, replacing damaged ones [14]. The proteins of the heart turn over at an average rate that would replace all proteins in the course of a month, although each protein has its own half-life [15].…”

Section: Introductionmentioning

confidence: 99%

Understanding the physiology of the ageing individual: computational modelling of changes in metabolism and endurance

2016

View full text Add to dashboard Cite

One contribution of 12 to a theme issue 'The Human Physiome: a necessary key to the creative destruction of medicine'. Ageing and lifespan are strongly affected by metabolism. The maximal possible uptake of oxygen is not only a good predictor of performance in endurance sports, but also of life expectancy. Figuratively speaking, healthy ageing is a competitive sport. Although the root cause of ageing is damage to macromolecules, it is the balance with repair processes that is decisive. Reduced or intermittent nutrition, hormones and intracellular signalling pathways that regulate metabolism have strong effects on ageing. Homeostatic regulatory processes tend to keep the environment of the cells within relatively narrow bounds. On the other hand, the body is constantly adapting to physical activity and food consumption. Spontaneous fluctuations in heart rate and other processes indicate youth and health. A (homeo)dynamic aspect of homeostasis deteriorates with age. We are now in a position to develop computational models of human metabolism and the dynamics of heart rhythm and oxygen transport that will advance our understanding of ageing. Computational modelling of the connections between dietary restriction, metabolism and protein turnover may increase insight into homeostasis of the proteins in our body. In this way, the computational reconstruction of human physiological processes, the Physiome, can help prevent frailty and age-related disease.

show abstract

“…The concept of the dynamic state of body constituents was first conceived by some scientists in the 19th and early 20th centuries (Guggenheim, 1991). This dynamic concept of metabolism, however, was not demonstrated with clear experimental evidence until Schoenheimer introduced the isotopic tracer technique (Schoenheimer & Rittenberg, 1935).…”

Section: Introductionmentioning

confidence: 99%

Advances in protein turnover analysis at the global level and biological insights

Li¹

2009

Mass Spectrometry Reviews

View full text Add to dashboard Cite

The concept of a dynamic state of body constituents, a precursor of the modern term of proteome dynamics, was conceived over a century ago. But, not until recently can we examine the dynamics of individual "constituents" for example, proteins at a truly global level. The path of advancement in our understanding of protein turnover at the global level is marked by the introduction of some key technological innovations. These methods include the isotopic tracer technique in the 1930s, the two-dimensional gel electrophoresis technique in the 1970s, the sector mass spectrometer that could analyze isotopomers of peptides in the early 1990s, the 2D gel/MALDI-TOF proteomics technology in the late 1990s, the booming liquid chromatography/mass spectrometry proteomics technology in this decade, and the recently emerging protein-tagging approaches that offer single-cell resolution for protein turnover measurements. The long-standing inquiry raised in the 1950s about the existence of a dynamic state in different organisms at different physiological conditions can now be answered with an individual "constituent" resolution on a truly global scale. Now it appears that protein degradation is not necessarily an end to the protein function. Rather, it can be the start of a new function because protein degradation clears the way for the action of other proteins. Protein turnover participates in a multi-layer complex regulatory network and shares equal importance with gene transcription and protein translation. The advances in technologies for protein turnover analysis and the improved understanding of the biological role of protein turnover will likely help to solve some long-standing biomedical problems such as the tuberculosis disease that at the present day still affects one-third of the world population.

show abstract

Rudolf Schoenheimer and the Concept of the Dynamic State of Body Constituents

Cited by 25 publications

References 5 publications

Atlas of Circadian Metabolism Reveals System-wide Coordination and Communication between Clocks

Atlas of Circadian Metabolism Reveals System-wide Coordination and Communication between Clocks

Understanding the physiology of the ageing individual: computational modelling of changes in metabolism and endurance

Advances in protein turnover analysis at the global level and biological insights

Contact Info

Product

Resources

About