Biology subjects

Pino, M. F.

Publications and source records attributed to Pino, M. F..

4 recordsLinked to original sources

bioRxiv2026

Multi-omic responses to acute exercise in abdominal subcutaneous adipose tissue of sedentary adults: findings from MoTrPAC

Exercise induces widespread health benefits across multiple tissues, yet the acute molecular responses in human adipose tissue remain poorly defined. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) profiled temporal molecular changes in abdominal subcutaneous adipose tissue (ASAT) following a single bout of exercise. Healthy sedentary adults were randomized to endurance (EE), resistance (RE), or control (CON) groups. ASAT biopsies were collected pre-exercise and at 45min, 4hr, and 24hr post-exercise, followed by transcriptomic, proteomic, phosphoproteomic, and metabolomic analyses. EE and RE elicited distinct, time-resolved molecular programs involving angiogenesis, extracellular matrix remodeling, mitochondrial metabolism, substrate utilization, and circadian regulation. Phosphoproteomics revealed acute changes in cytoskeletal and branched-chain amino acid metabolism proteins associated with glycemic control. Temporal metabolomic shifts were cell-type-specific. Finally, we identified candidate adipose-derived exerkines with predicted endocrine actions. This multi-omic map of acute ASAT responses offers insight into adipose-specific mechanisms by which exercise promotes metabolic health.

systems biology↗

bioRxiv2023

Comprehensive interrogation of human skeletal muscle reveals a dissociation between insulin resistance and mitochondrial capacity

Aims/HypothesisInsulin resistance and blunted mitochondrial capacity in skeletal muscle are often synonymous; however, this association remains controversial. The aim of this study was to perform an in-depth multi-factorial comparison of skeletal muscle mitochondrial capacity between individuals who were lean and active (Active), individuals with obesity (Obese) and individuals with Obesity, insulin resistance and type 2 diabetes (T2D). MethodsSkeletal muscle biopsies were obtained from the Vastus Lateralis of individuals who were lean and active (Active- n = 9), individuals with obesity (Obese- n = 9) and individuals with obesity insulin resistance and T2D (T2D- n =22) in this cross-sectional design. Mitochondrial capacity was assessed by ex vivo mitochondrial respiration with fatty-acid and glycolytic supported protocols adjusted for mitochondrial content (mtDNA and citrate synthase activity). Supercomplex assembly was measured by BN-PAGE and immunoblot. TCA cycle intermediates were assessed with targeted metabolomics. Exploratory transcriptomics and DNA methylation analyses were performed to uncover molecular differences affecting mitochondrial function among the three groups. ResultsActive had greater mitochondrial capacity compared to both Obese and T2D for ex vivo mitochondrial respiration with fatty-acid and glycolytic supported protocols adjusted for mitochondrial content (P < 0.05). Complex IV supercomplex assembley was greater in Active compared to Obese and T2D (P < 0.05) whereas Complex I and III supercomplex assembly was greater in Active compared to T2D only (P < 0.05). TCA cycle intermediates; citrate, succinate, fumarate and malate were all significantly greater in Active compared to Obese and T2D (P < 0.05). Strikingly, Obese and T2D do not differ in any of the skeletal muscle mitochondrial measurements. Active had an upregulation of genes related to respiration/mitochondrial capacity compared to both Obese and T2D. Transcriptional differences between Obese and T2D were not driven by mitochondrial related process. Active had reduced methylation correlated with increased gene expression for important mitochondrial-related genes, including ATP5PD and MFN2. Conclusions/InterpretationsWe reveal no discernable differences in skeletal muscle mitochondrial content, mitochondrial capacity and mitochondrial molecular profiles between obese individuals with and without T2D that had comparable levels of confounding factors (BMI, age, aerobic capacity) that affect mitochondrial capacity. We highlight that lean, active individuals have enhanced skeletal muscle mitochondrial capacity that is also reflected at the level of DNA methylation and gene transcription. The collective observation of comparable muscle mitochondrial capacity in individuals with obesity and T2D (vs. individuals without T2D) underscores a dissociation from skeletal muscle insulin resistance. Clinical trial numberNCT0191110

molecular biology↗

bioRxiv2022

The Presence of Myelinated Nerves and Schwann Cells in White Adipose Tissue: Proximity to Synaptic Vesicle Containing Nerve Terminals and Potential Role in BTBR ob/ob Demyelinating Diabetic Neuropathy

Peripheral neuropathy is a pathophysiological state of nerve degeneration and loss of tissue innervation. The most prominent cause of small fiber neuropathy is diabetes which can be demyelinating in nature, but this has not yet been explored in adipose tissue. Both demyelinating neuropathies and axonopathies implicate Schwann cells (SCs), the peripheral glial required for nerve myelination and regeneration after injury. Here, we perform a comprehensive assessment of SCs and myelination patterns of subcutaneous white adipose tissue (scWAT) nerves, including changes that occur with obesity and other imbalanced energy states in mice and humans. We found that mouse scWAT is densely innervated by both myelinated and unmyelinated sensory and sympathetic nerves. Accordingly, scWAT is home to both myelinating and non-myelinating SCs - the greater proportion of which are myelinating. Furthermore, SCs were found closely associated with synaptic vesicle-containing nerve terminals in scWAT. Obese BTBR ob/ob mice exhibit diabetic peripheral neuropathy in scWAT, and display concordant demyelination specific to small fibers, which was also associated with a decrease in the pan-SC marker Sox10 and compensatory increase in Krox20 gene expression. Together this suggests that adipose SCs may be involved in regulating the plasticity or the neuropathy of adipose tissue nerves.

neuroscience↗

bioRxiv2018

HDAC11 Suppresses the Thermogenic Program of Adipose Tissue via BRD2

Little is known about the biological function of histone deacetylase 11 (HDAC11), which is the lone class IV HDAC. Here, we demonstrate that deletion of HDAC11 in mice stimulates brown adipose tissue (BAT) formation and beiging of white adipose tissue (WAT). Consequently, HDAC11-deficient mice exhibit dramatically enhanced thermogenic potential and, in response to high fat feeding, attenuated obesity, insulin resistance, and hepatic steatosis. Ex vivo and cell-based assays revealed that HDAC11 catalytic activity suppresses the BAT transcriptional program, in both the basal state and in response to {beta}-adrenergic receptor signaling, through a mechanism that is dependent on physical association with BRD2, a bromodomain and extraterminal (BET) acetyl-histone binding protein. These findings define a novel epigenetic pathway for the regulation of energy homeostasis, and suggest potential for HDAC11-selective inhibitors for the treatment of obesity and diabetes.

molecular biology↗