bims-mimbat 2023-09-17 papers

Curr Opin Genet Dev. 2023 Sep 11. pii: S0959-437X(23)00092-8. [Epub ahead of print]83 102112

A new era of understanding in vivo metabolic flux in thermogenic adipocytes.

John A Haley, Cholsoon Jang, David A Guertin.

Nonshivering thermogenesis by brown adipose tissue (BAT) is an adaptive mechanism for maintaining body temperature in cold environments. BAT is critical in rodents and human infants and has substantial influence on adult human metabolism. Stimulating BAT therapeutically is also being investigated as a strategy against metabolic diseases because of its ability to function as a catabolic sink. Thus, understanding how brown adipocytes and the related brite/beige adipocytes use nutrients to fuel their demanding metabolism has both basic and translational implications. Recent advances in mass spectrometry and isotope tracing are improving the ability to study metabolic flux in vivo. Here, we review how such strategies are advancing our understanding of adipocyte thermogenesis and conclude with key future questions.

DOI: https://doi.org/10.1016/j.gde.2023.102112

Cell Rep. 2023 Sep 13. pii: S2211-1247(23)01143-9. [Epub ahead of print]42(9): 113131

Cold-stimulated brown adipose tissue activation is related to changes in serum metabolites relevant to NAD+ metabolism in humans.

Cold-induced brown adipose tissue (BAT) activation is considered to improve metabolic health. In murine BAT, cold increases the fundamental molecule for mitochondrial function, nicotinamide adenine dinucleotide (NAD+), but limited knowledge of NAD+ metabolism during cold in human BAT metabolism exists. We show that cold increases the serum metabolites of the NAD+ salvage pathway (nicotinamide and 1-methylnicotinamide) in humans. Additionally, individuals with cold-stimulated BAT activation have decreased levels of metabolites from the de novo NAD+ biosynthesis pathway (tryptophan, kynurenine). Serum nicotinamide correlates positively with cold-stimulated BAT activation, whereas tryptophan and kynurenine correlate negatively. Furthermore, the expression of genes involved in NAD+ biosynthesis in BAT is related to markers of metabolic health. Our data indicate that cold increases serum tryptophan conversion to nicotinamide to be further utilized by BAT. We conclude that NAD+ metabolism is activated upon cold in humans and is probably regulated in a coordinated fashion by several tissues.

Keywords: BAT; CP: Metabolism; NAD(+); cold exposure; human brown adipose tissue; nicotinamide; tryptophan

DOI: https://doi.org/10.1016/j.celrep.2023.113131

Biochim Biophys Acta Biomembr. 2023 Sep 11. pii: S0005-2736(23)00111-6. [Epub ahead of print]1866(1): 184229

Is the mitochondrial ATP synthesis solely H+-driven, K+,H+ symport-driven or K+/H+ antiport-driven?

Victor V Lemeshko.

Some recent literature experimental data indicate that the mitochondrial ATP synthesis might be not solely H+-driven, but K+,H+ symport-driven membrane potential-dependent, considered as a further development of Mitchell's chemiosmotic theory, in contrast to the anti-Mitchell's hypothesis of K+/H+ antiport-driven mechanism. In this short communication, the attention was pointed to a possible influence of the ionic strength of the used KCl incubation medium, versus of only K+ ions, and of the Mg2+-induced mitochondrial aggregation in the sucrose medium on the reported rates of the mitochondrial respiration and ATP synthesis. These observations were based on the own author's experimental works published earlier.

Keywords: Electrical neutrality principle; Energy coupling; FoF1-ATP synthase; Mitchell's chemiosmotic theory; Mitochondrial ATP synthesis

DOI: https://doi.org/10.1016/j.bbamem.2023.184229

Cell Metab. 2023 Sep 01. pii: S1550-4131(23)00300-5. [Epub ahead of print]

Seasonal light hours modulate peripheral clocks and energy metabolism in mice.

Lewin Small, Leonidas S Lundell, Jo Iversen, Amy M Ehrlich, Morten Dall, Astrid L Basse, Emilie Dalbram, Ann N Hansen, Jonas T Treebak, Romain Barrès, Juleen R Zierath.

Except for latitudes close to the equator, seasonal variation in light hours can change dramatically between summer and winter. Yet investigations into the interplay between energy metabolism and circadian rhythms typically use a 12 h light:12 h dark photoperiod corresponding to the light duration at the equator. We hypothesized that altering the seasonal photoperiod affects both the rhythmicity of peripheral tissue clocks and energy homeostasis. Mice were housed at photoperiods representing either light hours in summer, winter, or the equinox. Mice housed at a winter photoperiod exhibited an increase in the amplitude of rhythmic lipid metabolism and a modest reduction in fat mass and liver triglyceride content. Comparing melatonin-proficient and -deficient mice, the effect of seasonal light on energy metabolism was largely driven by differences in the rhythmicity of food intake and not melatonin. Together, these data indicate that seasonal light impacts energy metabolism by modulating the timing of eating.

Keywords: circadian biology; energy homeostasis; glucose metabolism; hormones; integrative physiology; obesity; transcriptomics

DOI: https://doi.org/10.1016/j.cmet.2023.08.005