A gerophysiology perspective on healthy ageing.

Improvements in public health and health care have resulted in significant increases in lifespan globally, but also in a significant increase in chronic disease prevalence. This has led to a focus on healthy ageing bringing a shift from a pathology-centered to an intrinsic capacity and function-centered view. In parallel, the emerging field of geroscience has promoted the exploration of the biomolecular drivers of ageing towards a transverse vision by proposing an integrated set of molecular hallmarks. In this review, we propose to take a step further in this direction, highlighting a gerophysiological perspective that considers the notion of homeostasis/allostasis relating to robustness/fragility respectively. While robustness is associated with homeostasis achieved by an optimal structure/function relationship in all organs, successive repair processes occurring after daily injuries and infections result in accumulation of scar healing leading to progressive tissue degeneration, allostasis and frailty. Considering biological ageing as the accumulation of scarring at the level of the whole organism emphasizes three transverse and shared elements in the body - mesenchymal stroma cells/immunity/metabolism (SIM). This SIM tryptich drives tissue and organ fate to regulate the age-related evolution of body functions. It provides the basis of a gerophysiology perspective, possibly representing a better way to decipher healthy ageing, not only by defining a composite biomarker(s) but also by developing new preventive/curative strategies.

Healthy Aging Biomarkers: The INSPIRE's Contribution.

The find solutions for optimizing healthy aging and increase health span is one of the main challenges for our society. A novel healthcare model based on integration and a shift on research and care towards the maintenance of optimal functional levels are now seen as priorities by the WHO. To address this issue, an integrative global strategy mixing longitudinal and experimental cohorts with an innovative transverse understanding of physiological functioning is missing. While the current approach to the biology of aging is mainly focused on parenchymal cells, we propose that age-related loss of function is largely determined by three elements which constitute the general ground supporting the different specific parenchyma: i.e. the stroma, the immune system and metabolism. Such strategy that is implemented in INSPIRE projects can strongly help to find a composite biomarker capable of predicting changes in capacity across the life course with thresholds signalling frailty and care dependence.

The INSPIRE Research Initiative: A Program for GeroScience and Healthy Aging Research Going from Animal Models to Humans and the Healthcare System.

Aging is the most important risk factor for the onset of several chronic diseases and functional decline. Understanding the interplays between biological aging and the biology of diseases and functional loss as well as integrating a function-centered approach to the care pathway of older adults are crucial steps towards the elaboration of preventive strategies (both pharmacological and non-pharmacological) against the onset and severity of burdensome chronic conditions during aging. In order to tackle these two crucial challenges, ie, how both the manipulation of biological aging and the implementation of a function-centered care pathway (the Integrated Care for Older People (ICOPE) model of the World Health Organization) may contribute to the trajectories of healthy aging, a new initiative on Gerosciences was built: the INSPIRE research program. The present article describes the scientific background on which the foundations of the INSPIRE program have been constructed and provides the general lines of this initiative that involves researchers from basic and translational science, clinical gerontology, geriatrics and primary care, and public health.

Towards a Large-Scale Assessment of the Relationship between Biological and Chronological Aging: The INSPIRE Mouse Cohort.

Aging is the major risk factor for the development of chronic diseases. After decades of research focused on extending lifespan, current efforts seek primarily to promote healthy aging. Recent advances suggest that biological processes linked to aging are more reliable than chronological age to account for an individual's functional status, i.e. frail or robust. It is becoming increasingly apparent that biological aging may be detectable as a progressive loss of resilience much earlier than the appearance of clinical signs of frailty. In this context, the INSPIRE program was built to identify the mechanisms of accelerated aging and the early biological signs predicting frailty and pathological aging. To address this issue, we designed a cohort of outbred Swiss mice (1576 male and female mice) in which we will continuously monitor spontaneous and voluntary physical activity from 6 to 24 months of age under either normal or high fat/high sucrose diet. At different age points (6, 12, 18, 24 months), multiorgan functional phenotyping will be carried out to identify early signs of organ dysfunction and generate a large biological fluids/feces/organs biobank (100,000 samples). A comprehensive correlation between functional and biological phenotypes will be assessed to determine: 1) the early signs of biological aging and their relationship with chronological age; 2) the role of dietary and exercise interventions on accelerating or decelerating the rate of biological aging; and 3) novel targets for the promotion of healthy aging. All the functional and omics data, as well as the biobank generated in the framework of the INSPIRE cohort will be available to the aging scientific community. The present article describes the scientific background and the strategies employed for the design of the INSPIRE Mouse cohort.

The INSPIRE Bio-Resource Research Platform for Healthy Aging and Geroscience: Focus on the Human Translational Research Cohort (The INSPIRE-T Cohort).

BACKGROUND: The Geroscience field focuses on the core biological mechanisms of aging, which are involved in the onset of age-related diseases, as well as declines in intrinsic capacity (IC) (body functions) leading to dependency. A better understanding on how to measure the true age of an individual or biological aging is an essential step that may lead to the definition of putative markers capable of predicting healthy aging. OBJECTIVES: The main objective of the INStitute for Prevention healthy agIng and medicine Rejuvenative (INSPIRE) Platform initiative is to build a program for Geroscience and healthy aging research going from animal models to humans and the health care system. The specific aim of the INSPIRE human translational cohort (INSPIRE-T cohort) is to gather clinical, digital and imaging data, and perform relevant and extensive biobanking to allow basic and translational research on humans. METHODS: The INSPIRE-T cohort consists in a population study comprising 1000 individuals in Toulouse and surrounding areas (France) of different ages (20 years or over - no upper limit for age) and functional capacity levels (from robustness to frailty, and even dependency) with follow-up over 10 years. Diversified data are collected annually in research facilities or at home according to standardized procedures. Between two annual visits, IC domains are monitored every 4-month by using the ICOPE Monitor app developed in collaboration with WHO. Once IC decline is confirmed, participants will have a clinical assessment and blood sampling to investigate markers of aging at the time IC declines are detected. Biospecimens include blood, urine, saliva, and dental plaque that are collected from all subjects at baseline and then, annually. Nasopharyngeal swabs and cutaneous surface samples are collected in a large subgroup of subjects every two years. Feces, hair bulb and skin biopsy are collected optionally at the baseline visit and will be performed again during the longitudinal follow up. EXPECTED RESULTS: Recruitment started on October 2019 and is expected to last for two years. Bio-resources collected and explored in the INSPIRE-T cohort will be available for academic and industry partners aiming to identify robust (set of) markers of aging, age-related diseases and IC evolution that could be pharmacologically or non-pharmacologically targetable. The INSPIRE-T will also aim to develop an integrative approach to explore the use of innovative technologies and a new, function and person-centered health care pathway that will promote a healthy aging.

Glucose and hypothalamic astrocytes: More than a fueling role?

Brain plays a central role in energy homeostasis continuously integrating numerous peripheral signals such as circulating nutrients, and in particular blood glucose level, a variable that must be highly regulated. Then, the brain orchestrates adaptive responses to modulate food intake and peripheral organs activity in order to achieve the fine tuning of glycemia. More than fifty years ago, the presence of glucose-sensitive neurons was discovered in the hypothalamus, but what makes them specific and identifiable still remains disconnected from their electrophysiological signature. On the other hand, astrocytes represent the major class of macroglial cells and are now recognized to support an increasing number of neuronal functions. One of these functions consists in the regulation of energy homeostasis through neuronal fueling and nutrient sensing. Twenty years ago, we discovered that the glucose transporter GLUT2, the canonical "glucosensor" of the pancreatic beta-cell together with the glucokinase, was also present in astrocytes and participated in hypothalamic glucose sensing. Since then, many studies have identified other actors and emphasized the astroglial participation in this mechanism. Growing evidence suggest that astrocytes form a complex network and have to be considered as spatially coordinated and regulated metabolic units. In this review we aim to provide an updated view of the molecular and respective cellular pathways involved in hypothalamic glucose sensing, and their relevance in physiological and pathological states.

The corticotrophin-releasing factor/urocortin system regulates white fat browning in mice through paracrine mechanisms.

OBJECTIVES: The corticotrophin-releasing factor (CRF)/urocortin system is expressed in the adipose tissue of mammals, but its functional role in this tissue remains unknown. METHODS: Pharmacological manipulation of the activity of CRF receptors, CRF1 and CRF2, was performed in 3T3L1 white pre-adipocytes and T37i brown pre-adipocytes during in vitro differentiation. The expression of genes of the CRF/urocortin system and of markers of white and brown adipocytes was evaluated along with mitochondrial biogenesis and cellular oxygen consumption. Metabolic evaluation of corticosterone-deficient or supplemented Crhr1-null (Crhr1(-/-)) mice and their wild-type controls was performed along with gene expression analysis carried out in white (WAT) and brown (BAT) adipose tissues. RESULTS: Peptides of the CRF/urocortin system and their cognate receptors were expressed in both pre-adipocyte cell lines. In vitro pharmacological studies showed an inhibition of the expression of the CRF2 pathway by the constitutive activity of the CRF1 pathway. Pharmacological activation of CRF2 and, to a lesser extent, inhibition of CRF1 signaling induced molecular and functional changes indicating transdifferentiation of white pre-adipocytes and differentiation of brown pre-adipocytes. Crhr1(-/-) mice showed increased expression of CRF2 and its agonist Urocortin 2 in adipocytes that was associated to brown conversion of WAT and activation of BAT. Crhr1(-/-) mice were resistant to diet-induced obesity and glucose intolerance. Restoring physiological circulating corticosterone levels abrogated molecular changes in adipocytes and the favorable phenotype of Crhr1(-/-) mice. CONCLUSIONS: Our findings suggest the importance of the CRF2 pathway in the control of adipocyte plasticity. Increased CRF2 activity in adipocytes induces browning of WAT, differentiation of BAT and is associated with a favorable metabolic phenotype in mice lacking CRF1. Circulating corticosterone represses CRF2 activity in adipocytes and may thus regulate adipocyte physiology through the modulation of the local CRF/urocortin system. Targeting CRF receptor signaling specifically in the adipose tissue may represent a novel approach to tackle obesity.

Sensory-specific satiety for a food is unaffected by the ad libitum intake of other foods during a meal. Is SSS subject to dishabituation?

Sensory-specific satiety (SSS) is defined as a decrease in the pleasantness of a specific food that has just been eaten to satiation, while other non-eaten foods remain pleasant. The objectives of this study were the following: (1) to investigate whether SSS for a food is affected by the ad libitum intake of other foods presented sequentially during a meal, (2) to compare the development of SSS when foods are presented simultaneously or sequentially during a meal, and (3) to examine whether SSS is modified when foods are presented in an unusual order within a meal. Twelve participants participated in three tasting sessions. In session A, SSS for protein-, fat- and carbohydrate-rich sandwiches was measured after the ad libitum consumption of single type of each of these foods. In session B, SSS was measured for the same three foods consumed ad libitum but presented simultaneously. Session C was identical to session A, except that the presentation order of the three foods was reversed. The results indicate that once SSS for a given food is reached, the ad libitum consumption of other foods with different sensory characteristics does not decrease SSS, regardless of the order in which the foods are presented. Once reached, SSS is thus not subject to dishabituation during a meal.

Pro-inflammatory phospholipid arachidonic acid/eicosapentaenoic acid ratio of dysmetabolic severely obese women.

BACKGROUND: Fatty acids (FAs) and adipokines such as adiponectin or interleukin-6 (IL-6) are known to modulate inflammation and the development of metabolic syndrome. Whether FA composition assessed in plasma triacylglycerols (TAGs), phospholipids (PLs) and non-esterified fatty acids (NEFAs) and adipose tissue (AT) PLs differed between dysmetabolic and non-dysmetabolic severely obese women remains to be established. Whether the plasma and/or AT arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio in the PL sub-fraction may be associated with adipokine AT gene expression needs to be examined. METHODS: FA composition was measured in plasma lipid classes and in the TAG and PL sub-fractions of subcutaneous abdominal and omental ATs of severely obese women paired for age and adiposity but showing a dysmetabolic profile (n = 13) or not (n = 14). FA profile was assessed by gas chromatography. Plasma and AT mRNA concentrations of adiponectin and IL-6 were measured by ELISA and real-time polymerase chain reaction, respectively. RESULTS: Plasma adiponectin and FA concentrations in the NEFA sub-fraction were, respectively, lower and higher in dysmetabolic than in non-dysmetabolic women (p < 0.05). Despite similar FA levels in the PL sub-fraction, the AA/EPA ratio was higher in plasma and ATs (p < 0.005), because of an EPA decrease in plasma and subcutaneous abdominal fat vs. an AA increase in the omental depot. The AA/EPA ratio was negatively associated with adiponectin concentrations in plasma and subcutaneous abdominal AT (0.01 < p < 0.05). CONCLUSIONS: Metabolic dysfunction is associated with a pro-inflammatory phospholipid AA/EPA ratio in plasma and ATs, and an altered adiponectin secretion that could contribute to developing metabolic syndrome.

Relationships between adipose tissues and brain: what do we learn from animal studies?

Over the last decades, more and more data supporting the importance of the relationships between the brain and adipose tissues (white and brown) in regards of body weight regulation and energy homeostasis have been published. Indeed the brain via the autonomic nervous system participates to the regulation of different parameters such as the metabolic (lipolysis, lipogenesis and thermogeneis), and secretory (leptin and other adipokines) activities but also plasticity (proliferation differentiation and apoptosis) of adipose tissues. In turn the various fat pads will send information via sensory innervation of white adipose tissue as well as metabolic and hormonal signals acting directly on some brain areas. Altogether these results showed the presence of a neural feedback loop between adipose tissues and the brain which plays a major role in the regulation of energy homeostasis and as been shown to vary according to physiological and pathological states.

Adipose tissue lymphocytes: types and roles

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Besides adipocytes, specialized in lipid handling and involved in energy balance regulation, white adipose tissue (WAT) is mainly composed of other cell types among which lymphocytes represent a non-negligible proportion. Different types of lymphocytes (B, alphabetaT, ãäT, NK and NKT) have been detected in WAT of rodents or humans, and vary in their relative proportion according to the fat pad anatomical location. The lymphocytes found in intra-abdominal, visceral fat pads seem representative of innate immunity, while those present in subcutaneous fat depots are part of adaptive immunity, at least in mice. Both the number and the activity of the different lymphocyte classes, except B lymphocytes, are modified in obesity. Several of these modifications in the relative proportions of the lymphocyte classes depend on the degree of obesity, or on leptin concentration, or even fat depot anatomical location. Recent studies suggest that alterations of lymphocyte number and composition precede the macrophage increase and the enhanced inflammatory state of WAT found in obesity. Lymphocytes express receptors to adipokines while several proinflammatory chemokines are produced in WAT, rendering intricate crosstalk between fat and immune cells. However, the evidences and controversies available so far are in favour of an involvement of lymphocytes in the control of the number of other cells in WAT, either adipocytes or immune cells and of their secretory and metabolic activities. Therefore, immunotherapy deserves to be considered as a promising approach to treat the endocrino-metabolic disorders associated to excessive fat mass development (AU)

Constitutive expression of suppressor of cytokine signalling-3 in skeletal muscle leads to reduced mobility and overweight in mice.

AIMS/HYPOTHESIS: Due to their ability to regulate various signalling pathways (cytokines, hormones, growth factors), the suppressor of cytokine signalling (SOCS) proteins are thought to be promising therapeutic targets for metabolic and inflammatory disorders. Hence, their role in vivo has to be precisely determined. METHODS: We generated transgenic mice constitutively producing SOCS-3 in skeletal muscle to define whether the sole abundance of SOCS-3 is sufficient to induce metabolic disorders and whether SOCS-3 is implicated in physiological roles distinct from metabolism. RESULTS: We demonstrate here that chronic expression of SOCS-3 in skeletal muscle leads to overweight in mice and worsening of high-fat diet-induced systemic insulin resistance. Counter-intuitively, insulin sensitivity in muscle of transgenic mice appears to be unaltered. However, following constitutive SOCS-3 production, several genes had deregulated expression, among them other members of the SOCS family. This could maintain the insulin signal into skeletal muscle. Interestingly, we found that SOCS-3 interacts with calcineurin, which has been implicated in muscle contractility. In Socs-3 transgenic muscle, this leads to delocalisation of calcineurin to the fibre periphery. Relevant to this finding, Socs-3 transgenic animals had dilatation of the sarcoplasmic reticulum associated with swollen mitochondria and decreased voluntary activity. CONCLUSIONS/INTERPRETATION: Our results show that constitutive SOCS-3 production in skeletal muscle is not in itself sufficient to induce the establishment of metabolic disorders such as diabetes. In contrast, we reveal a novel role of SOCS-3, which appears to be important for muscle integrity and locomotor activity.

Possible common central pathway for resistin and insulin in regulating food intake.

AIM: Adipose tissue has been the object of intense research in the field of obesity and diabetes diseases in the last decade. Examination of adipocyte-secreted peptides led to the identification of a unique polypeptide, resistin (RSTN), which has been suggested as a link between obesity and diabetes. RSTN plays a clearly documented role in blocking insulin (INS)-induced hypoglycaemia. As brain injection of INS affects feeding behaviour, we studied the possible interaction between INS and RSTN in food-deprived rats, measuring effects on food intake. In addition, we examined how RSTN might affect neuropeptide Y (NPY)-induced feeding, as studies have shown that rat RSTN can interfere with the NPY system. METHODS: Overnight food-deprived rats were injected into the third brain ventricle (3V) with either INS (10 or 20 mUI), RSTN (0.1-0.4 nmol/rat), or saline before access to food. Another group of rats was injected into the 3V with RSTN alone, NPY alone or RSTN plus NPY. Their food intake and body weight were measured. RESULTS: Our results confirm the hypophagic effect of RSTN on food deprivation-induced food intake, and more importantly, show that RSTN neither potentiates nor blocks the effects of INS on food intake, but does reduce the hyperphagic effect of NPY. CONCLUSION: The observation that RSTN does not modify feeding INS-induced hypophagia, but does influence NPY-induced feeding, points to the possibility that RSTN may be involved in control of food intake through an NPY-ergic mechanism as INS.

Coadministration of coenzyme Q prevents rosiglitazone-induced adipogenesis in ob/ob mice.

OBJECTIVE: The aim of this study is to determine the effect of coenzyme Q (Q) on ob/ob mice treated or not with thiazolidinedione (TZD). DESIGN AND MEASUREMENTS: Ob/ob mice were treated with Q, Rosiglitazone or a combination of both molecules for 13 days; physical and metabolic parameters as well as oral glucose tolerance test were assessed. mRNA expression of genes of energy dissipation and storage were measured by real-time PCR. RESULTS: Q treatment improved some metabolic parameters in ob/ob mice. Surprisingly, cotreatment with Rosiglitazone and Q improved metabolic parameters and prevented TZD increase in body weight and adiposity, mainly by increasing lipid oxidation in adipose tissue, reducing lipid synthesis and balancing adipokine gene expression. CONCLUSIONS: Our finding suggests that Rosiglitazone and coenzyme Q bitherapy could prevent the body weight gain associated with adipogenesis and could improve the clinical use of these compounds.

Adiponectin receptors are expressed in hypothalamus and colocalized with proopiomelanocortin and neuropeptide Y in rodent arcuate neurons.

Adiponectin is involved in the control of energy homeostasis in peripheral tissues through Adipor1 and Adipor2 receptors. An increasing amount of evidence suggests that this adipocyte-secreted hormone may also act at the hypothalamic level to control energy homeostasis. In the present study, we observed the gene and protein expressions of Adipor1 and Adipor2 in rat hypothalamus using different approaches. By immunohistochemistry, Adipor1 expression was ubiquitous in the rat brain. By contrast, Adipor2 expression was more limited to specific brain areas such as hypothalamus, cortex, and hippocampus. In arcuate and paraventricular hypothalamic nuclei, Adipor1, and Adipor2 were expressed by neurons and astrocytes. Furthermore, using transgenic green fluorescent protein mice, we showed that Adipor1 and Adipor2 were present in pro-opiomelanocortin (POMC) and neuropeptide Y (NPY) neurons in the arcuate nucleus. Finally, adiponectin treatment by intracerebroventricular injection induced AMP-activated protein kinase (AMPK) phosphorylation in the rat hypothalamus. This was confirmed by in vitro studies using hypothalamic membrane fractions. In conclusion, Adipor1 and Adipor2 are both expressed by neurons (including POMC and NPY neurons) and astrocytes in the rat hypothalamic nuclei. Adiponectin is able to increase AMPK phosphorylation in the rat hypothalamus. These data reinforced a potential role of adiponectin and its hypothalamic receptors in the control of energy homeostasis.

Adipose tissue lymphocytes: types and roles.

Besides adipocytes, specialized in lipid handling and involved in energy balance regulation, white adipose tissue (WAT) is mainly composed of other cell types among which lymphocytes represent a non-negligible proportion. Different types of lymphocytes (B, alphabetaT, gammadeltaT, NK and NKT) have been detected in WAT of rodents or humans, and vary in their relative proportion according to the fat pad anatomical location. The lymphocytes found in intra-abdominal, visceral fat pads seem representative of innate immunity, while those present in subcutaneous fat depots are part of adaptive immunity, at least in mice. Both the number and the activity of the different lymphocyte classes, except B lymphocytes, are modified in obesity. Several of these modifications in the relative proportions of the lymphocyte classes depend on the degree of obesity, or on leptin concentration, or even fat depot anatomical location. Recent studies suggest that alterations of lymphocyte number and composition precede the macrophage increase and the enhanced inflammatory state of WAT found in obesity. Lymphocytes express receptors to adipokines while several proinflammatory chemokines are produced in WAT, rendering intricate crosstalk between fat and immune cells. However, the evidences and controversies available so far are in favour of an involvement of lymphocytes in the control of the number of other cells in WAT, either adipocytes or immune cells and of their secretory and metabolic activities. Therefore, immunotherapy deserves to be considered as a promising approach to treat the endocrino-metabolic disorders associated to excessive fat mass development.

Reg genes are CCK2 receptor targets in ElasCCK2 mice pancreas.

We previously demonstrated that expression of the gastrin receptor, CCK2R, in pancreatic acini of transgenic ElasCCK2 mice induced alteration of acinar morphology and differentiation, increased sensitivity to a carcinogen and development of preneoplastic lesions and tumours. Reg proteins are suggested to be involved in pancreatic cancer and in regeneration of endocrine pancreas. Reg I gene is a known target of gastrin. We examined whether an expression of CCK2R in the pancreatic acini of ElasCCK2 mice is linked to induction of Reg proteins expression. We analyzed Reg expression by Western-blot and immunohistochemistry in pancreas from ElasCCK2 and control mice. Islet neogenesis, glucose homeostasis, insulin secretion and content were also evaluated. Reg I is exclusively produced in acini in ElasCCK2 and control mice. In tumoral pancreas, Reg I and Reg III proteins are expressed in duct-like cells in preneoplastic lesions or in the periphery of tumours and in adjacent acini. The expression of Reg III proteins is increased in ElasCCK2 pancreas before the development of preneoplastic lesions in a subpopulation of islet cells and in small islet-like cell clusters dispersed within the acinar tissue. Several criteria of an enhanced neogenesis are fulfilled in ElasCCK2 pancreas. Moreover, ElasCCK2 mice have an improved response to glucose load, an increased insulin secretion and a doubling of insulin content compared to control mice. We show that Reg proteins are targets of CCK2R activation and are induced during early steps of carcinogenesis in ElasCCK2 mice pancreas. Alterations of exocrine tissue homeostasis in ElasCCK2 pancreas concomitantly activate regenerative responses of the endocrine pancreas possibly linked to paracrine actions of Reg III proteins.

Weight-dependent changes of immune system in adipose tissue: importance of leptin.

Ancestral lymphoid cells reside in adipose tissues, and their numbers are highly altered in obesity. Leptin, production of which is correlated to fat mass, is strongly involved in the relationships between adipose tissues and immune system. We investigated in epididymal (EPI) and inguinal (ING) fat pads to determine whether 1) lymphocyte phenotypes were correlated to the tissue weight and 2) leptin was involved in such relationships. Immunohistological analyses revealed a tight relationship between the T and NK lymphocytes of the stromal vascular fraction and adipocytes. We identified a significant negative and positive correlation between EPI weight and the percentage of NK and total T cells respectively by cytofluorometric analyses. The NK and ancestral gammadelta T cell contents were directly dependent of leptin since they increased significantly in high-fat (HF) diet mice but not in leptin-deficient (ob/ob) mice as compared to control. By contrast, the alphabeta T cell content seemed independent of leptin because their percentages increased significantly with the EPI weight whatever the type of mice (control, HF, ob/ob). The present study suggests that adipose tissues present, according to their localization, different immunological mechanisms that might be involved in the regulation of adipose cells functions and proliferations.

Plasticity of adipose tissue: a promising therapeutic avenue in the treatment of cardiovascular and blood diseases?

The adipose tissue represents a large amount of adult tissues. For long time, it was considered as a poorly active overgrown and undesirable tissue even if its usefulness was demonstrated in reconstructive surgery. It was studied for its main involvement in energy metabolism and disorders as diabetes and obesity. More recently, its endocrine functions emerged and appeared to play a key role in many physiological situations such as inflammation and immunity. The presence of preadipocytes throughout life was demonstrated using primary culture technology from cells derived from adipose tissue. These cells can display a macrophagic or endothelial potential according to their environment and could be now considered as vascular progenitors. Differentiation of various adipose derived cell subsets towards functional cardiomyocytes, osteoblasts, haematopoietic and neural cells was also obtained in vitro. Altogether, these data emphasise the need to consider with a new look preadipocyte status and adipose tissue biology. These spectacular data, together with the fact that adipose tissue is easy to obtain lead to numerous and promising perspectives in regenerative medicine. They highlight the concept that progenitor cells from adipose tissue constitute an alternative for cells-based strategies designed for the treatment of cardiovascular diseases.