The potential of cannabinoids in managing cancer-related anorexia in older adults: a systematic review of the literature.

BACKGROUND AND OBJECTIVES: Anorexia of aging (AoA) is a prevalent geriatric syndrome characterized by a multifactorial decline in appetite and reduced food intake associated with the aging process. This systematic review aims to investigate the use and outcomes of cannabinoids in addressing AoA, with the goal of providing a comprehensive understanding and discussing their potential integration into daily clinical practice. METHODS: A thorough search of databases (Embase Ovid, Scopus, PubMed, Cochrane Library, and Web of Science) identified 6100 studies. After eliminating duplicates and screening titles and abstracts, 25 studies underwent full appraisal. Two reviewers assessed inclusion suitability, and study methodologies were evaluated using the Newcastle-Ottawa Scale (NOS) for observational studies and the modified Jadad Scoring Scale for randomized controlled trials. Ultimately, six studies published between 2002 and 2019, involving 869 participants, were included in the review. RESULTS: Out of the 6 fin. l papers selected, 5 were randomized trials, and 1 was a prospective study. Megestrol acetate (800 mg/d) proved to be more effective than dronabinol 2.5 mg twice a day in increasing appetite. Nabilone (at a dosage of 0.5 mg per day) did not show superiority over placebo in alleviating symptoms such as pain, nausea, loss of appetite, and weight. However, with a double dosage followed by 1.0 mg/6 weeks, after eight weeks of treatment, patients recorded a significant increase in calorie intake and carbohydrate consumption compared to the placebo group, with some patients also experiencing substantial weight gain. Regarding delta-9-tetrahydrocannabinol (THC), a weight increase of ≥10% was observed in 17.6% of patients with doses of 5 mg or 10 mg capsules daily, without significant side effects. Additionally, patients treated with THC 2.5 mg reported improved chemosensory perception and increased appetite before meals compared to placebo. No significant side effects were reported in older adults taking cannabinoids. CONCLUSIONS: Cannabinoids offer promise in enhancing the quality of life for older individuals with active neoplastic disease. However, to establish comprehensive guidelines, further research with larger sample sizes is essential. Only through this approach can we fully grasp the potential and application of cannabinoids in addressing the nutritional concerns associated with neoplastic diseases.

Use of different anticholinergic scales and their correlation with anticholinergic symptom burden in a cohort of people living with HIV.

OBJECTIVES: How to detect the clinical impact of anticholinergic (AC) burden in people with HIV (PWH) remains poorly investigated. We cross-sectionally described the prevalence and type of AC signs/symptoms and the screening accuracy of three AC scales in detecting their presence in a modern cohort of PWH. METHODS: We calculated AC Burden Scale (ABS), AC Risk Score (ARS) and AC Drug Score (ADS) in 721 adult PWH and recorded the presence of AC signs/symptoms over the previous 3 months. High AC risk was defined by ABS score ≥2, and ARS or ADS score ≥3. Comparisons among the scale were based on Cohen's inter-rater agreement, and their screening accuracy was assessed by receiver operating characteristics (ROC) curves and performance measures. RESULTS: We enrolled 721 PWH, of whom 72.0% of participants were male; the median age was 53 years, and 164 participants (22.7%) were on at least one AC drug. Among these, 28.6% experienced at least one AC sign/symptom. Agreement in AC risk classification was substantial only between ARS and ADS (k = 0.6). Lower and higher risk of AC signs/symptoms was associated with dual regimens [adjusted OR (aOR) = 0.12 versus three-drug regimens, P = 0.002] and increasing number of AC drugs (aOR = 12.91, P < 0.001). Depression and COPD were also associated with higher risk of AC signs/symptoms in analysis unadjusted for number of AC drugs. ABS and ADS showed the best area under the ROC curve (AUROC) of 0.85 (0.78-0.92) and 0.84 (0.75-0.92; P < 0.001 for both). However, at the cut-off used for the general population, the sensitivity of all three scales was very low (34.0%, 46.8% and 46.8%). CONCLUSIONS: Up to one-fourth of participants in our cohort were exposed to at least one AC drug, and among them AC signs/symptoms affected more than one-fourth. Both polypharmacy (as number of antiretrovirals and of co-medications with AC properties) and to a lesser extent specific comorbidities shaped the risk of developing AC signs/symptoms. Sensitive screenings for AC risk in PWH should prefer ABS or ADS based on lower cut-offs than those suggested for the general population.

Functional autonomy and 12-month mortality in older adults with proximal femoral fractures in an orthogeriatric setting: risk factors and gender differences.

BACKGROUND: Proximal femur fractures have a negative impact on loss of functional autonomy and mortality. OBJECTIVE: The aim of this retrospective study was to evaluate functional autonomy and mortality in a group of older adults with hip fractures managed in an orthogeriatric setting 12 months after discharge and to determine if gender affected outcome. METHODS: In all participants, we assessed clinical history, functional pre-fracture status using activities of daily living (ADL) and in-hospital details. At 12 months after discharge, we evaluated functional status, place of residence, hospital readmissions and mortality. RESULTS: We studied 361 women and 124 men and we observed a significant reduction in the ADL score at 6 months (1.15 ± 1.58/p < 0.001 in women and 1.45 ± 1.66/p < 0.001 in men). One-year mortality (33.1% in men and 14.7% in women) was associated with pre-fracture ADL score and reduction in ADL at 6 months (HR 0.68/95%, CI 0.48-0.97/p < 0.05 and HR 1.70/95%, CI 1.17-2.48/p < 0.01, respectively) in women, and new hospitalisations at 6 months and polypharmacy in men (HR 1.65/95%, CI 1.07-2.56/p < 0.05 and HR 1.40/95%, CI 1.00-1.96/p = 0.05, respectively) in Cox's regression model. DISCUSSION AND CONCLUSIONS: Our study suggests that functional loss in older adults hospitalised for proximal femur fractures is greatest in the first 6 months after discharge, and this increases the risk of death at 1 year. Cumulative mortality at 12 months is higher in men and appears to be related to polypharmacy and new hospital admissions 6 months after discharge.

Surgical aortic valve replacement in elderly patients: effects on physical performance, cognitive function and health-related quality of life.

BACKGROUND: Surgical aortic valve replacement (SAVR) is still the gold standard for treating aortic valve stenosis (AVS). Its effectiveness has been extensively examined in terms of perioperative mortality, but its impact on overall health has received much less attention. AIMS: To assess the physical performance, cognitive status, and health-related quality of life of elderly patients undergoing SAVR, in the short, medium and long term. METHODS: This single-center prospective study enrolled patients aged > 70 years who underwent isolated SAVR for severe AVS. Data were collected on each participant's clinical status, physical performance, cognitive status, mood, and health-related quality of life. This multidimensional geriatric assessment was performed before surgery (T0), and again at 45 days (T1), 3 months (T2), 6 months (T3), and 12 months (T4) post-surgery. Baseline (T0) and follow-up (T2-T4) data were compared separately for patients grouped by gender using paired t-tests. RESULTS: Data from a total of 35 patients were analyzed. Compared with the baseline (T0), nutritional status worsened at T1, then gradually improved through to T4. Physical performance, mood, and health-related quality of life improved significantly after surgery. Cognitive function showed no change through to T3, but then deteriorated at T4. CONCLUSIONS: Our results show that SAVR in patients over 70 years of age has a positive impact on nutrition, mood, and health-related quality of life. Cognitive function was not negatively affected in the short and medium term, although it deteriorated in the long term. SAVR also had a positive impact on the physical performance of our sample.

Serum 25-Hydroxyvitamin D and the Incidence of Peripheral Artery Disease in the Elderly: The Pro.V.A Study.

AIM: This study was conducted to examine whether low serum levels of 25-hydroxyvitamin D (25OHD)are associated with a higher risk of incident peripheral artery disease (PAD) in a representative group of elderly people. METHODS: We followed 1568 community-dwelling elderly participants without PAD at the baseline (among a sample of 2097 initially eligible) over a mean of 4.4 years as part of the Progetto Veneto Anziani (Pro.V.A.) study. The baseline serum 25OHD levels were categorized as ＜24, 25-49, 50-74, ＞75 nmol/L, and incident PAD was defined as an ankle-brachial index below 0.9. RESULTS: At the baseline, there were no differences in known risk factors for PAD (BMI, waist circumference, diabetes, cardiovascular diseases, smoking habits, total cholesterol) or in the ankle-brachial index (ABI) between the groups with different serum 25OHD levels (＜24, 25-49, 50-74, ＞75 nmol/L). During a 4.4-year follow-up, 371 subjects developed PAD. The group with serum 25OHD levels ＞75 nmol/L was set as the reference group, and an adjusted Cox's regression analysis showed no association between low vitamin D levels and incident PAD during the follow-up: the hazard ratio ranged from 0.76 (95%CI: 0.41-1.42) for participants with serum 25OHD levels below 25 nmol/L to 1.32 (95%CI: 0.72-2.39) for those with serum 25OHD levels between 50-74 nmol/L (p for trend=0.08). These results did not change when participants were stratified by several risk factors for PAD. CONCLUSIONS: Baseline hypovitaminosis D did not predict the onset of PAD over a 4.4-year follow-up in elderly people.

Long-term outcome of morphology and function after soft tissue injury of the forearm with vascular involvement.

BACKGROUND: We sought to assess long-term changes in bone, muscle area, and muscle strength at different levels of the forearm and hand mobility according to arterial patency and nerve damage after surgically treated trauma related to involuntary local cutting/piercing injuries. METHODS: Forty subjects were evaluated 11 years after surgery for traumatic lesions involving the major vascular axis of the distal forearm. Peripheral quantitative computed tomography was used to measure cortical bone mineral density (BMD) and muscle area at the proximal radius, trabecular BMD at the distal radius, and cortical BMD at the third finger. Hand grip strength was assessed using dynamometry. Muscle area and hand grip strength were corrected for the limb dominance effect. RESULTS: All subjects had reduced trabecular BMD at the distal radius on the affected side (Δ, -5.8%; P < 0.001) and reduced cortical BMD in the third finger (Δ, -2.8%; P < 0.05). Hand grip strength was significantly lower on the affected side. According to vascular patency, only subjects with nonpreserved blood flow had significantly reduced distal radius BMD (Δ, -6.7%; P = 0.004), and those with nerve damage had a significant reduction in BMD at the third finger (Δ, -3.5%; P = 0.05). Moreover, nerve injury was associated with the presence of clinical symptoms and hand functional impairment. CONCLUSIONS: The absence of blood flow and nerve damage after forearm trauma caused by involuntary cutting/piercing injuries causes remarkable permanent impairment in musculoskeletal structures, hand grip strength, and hand functionality.

Preventive effect of risedronate on bone loss and frailty fractures in elderly women treated with anastrozole for early breast cancer.

The aim of this study was to assess the effect of adjuvant anastrozole, alone or associated with risedronate, on BMD and bone fracture risk in women more than 70 years old with hormone receptor-positive early breast cancer (EBC). In a group of 51 elderly women (aged 76.4 ± 5.0 years) considered for adjuvant aromatase inhibitors for EBC, 24 patients with T-scores ≥ -2 and no prevalent fractures received anastrozole 1 mg/day (group A), and 27 patients with T-scores < -2, or with T-scores ≥ -2 and prevalent fractures (group B), received anastrozole (1 mg/day) plus risedronate (35 mg/week). Both groups received supplementation with 1 g calcium carbonate and 800 IU vitamin D per day. Differences in BMD and frailty fractures were evaluated after 1 and 2 years. In group A, significant decreases in BMD were observed in the lumbar spine (Δ BMD, -0.030 ± 0.04 g/cm², P < 0.05), femoral neck (Δ BMD, -0.029 ± 0.05 g/cm², P < 0.05), and trochanter (Δ BMD, -0.026 ± 0.03 g/cm², P < 0.01) after 2 years. The greatest percent reduction in height (Hpr) emerged in the thoracic spine (3.6 ± 2.4%, P < 0.01), although only one incident vertebral fracture was observed. In group B, BMD increased in the lumbar spine (Δ BMD, 0.038 ± 0.04, P < 0.001), although no significant changes were seen in the hip regions. The decline in Hpr was negligible (about 1%). No incident fractures were observed at follow-up. In conclusion, anastrozole treatment for EBC in elderly women seems to have only mild negative effects on the femoral bone. Risedronate makes the use of anastrozole safer, even for osteopenic or osteoporotic elderly patients.

Traumatic musculoskeletal changes in forearm and hand after emergency vascular anastomosis or ligation.

Whether the best option for the emergency treatment of major forearm artery lesions is anastomosis or ligation is still debated in the literature. The choice may be influenced by the resulting long-term musculoskeletal changes relating to vessel patency and the surgical procedure used. Fifty-three patients who had undergone emergency surgery involving arterial microanastomoses for lesions affecting one or more major forearm arteries (with a preserved distal circulation) were reassessed in terms of anastomosis patency at the end of a long-term follow-up, using arterial plethysmography, eco-color Doppler, and magnetic resonance angiography. In a subset of 40 patients, changes in bone mineral density (BMD) and lean mass of the affected limb were compared with the contralateral healthy limb and correlated with vessel patency and severity of trauma, using peripheral quantitative computed tomography and dual X-ray absorptiometry. Functional performance was also tested with a dynamometer by means of the hand-grip test. At long-term reassessment, 75% of the microanastomosed vessels were patent. BMD showed significant impairments at and around the site of the lesion (Delta: -6%, P < 0.001) and distally thereto (Delta: -3%, P < 0.05), which correlated with vessel occlusion and trauma severity. The fracture risk consequently also increased. There was evidence of a significant loss of lean mass ( P < 0.01) and muscle strength in the affected limb, especially in cases of occlusion of a major vessel. Given the satisfactory outcome of the anastomotic procedures as opposed to the greater loss of bone mass, muscular mass, and strength in patients who had undergone arterial ligation, we suggest that anastomosis is always preferable to ligation, even in emergencies. Anastomosis enables overall limb function to be better preserved (both in the vicinity of the lesion and distally).

Predictors of low bone mineral density in elderly males with chronic obstructive pulmonary disease: the role of body mass index.

OBJECTIVE: The aim of this study was to investigate the relationships between nutritional indices (Body mass index (BMI), serum albumin), sarcopenia, bone mineral density (BMD) and the severity of their pulmonary obstruction in elderly patients with chronic obstructive pulmonary disease (COPD). METHODS: The method involved was a prospective transversal study; 82 males >65 years old, 41 stable patients with COPD and 41 healthy elderly individuals (controls). All subjects underwent spirometry, biochemical analyses and dual energy X-ray absorptiometry. The significance of the differences between mean values and prevalence rates was tested. The relationships between BMD and independent predictors were analysed by multiple linear regressions. Logistic regression models were applied on dichotomised variables. RESULTS: In patients with COPD, the prevalence of osteoporosis was higher in subjects with sarcopenia (46% vs. 0%; p < 0.05) and with BMI < 25.1 kg/m(2) (58% vs. 15%; p < 0.02). Multiple regression analysis indicated that BMI, appendicular skeletal muscle mass (ASMM), albumin, and forced expiration volume after 1 s (FEV1) explained the 70% of BMD variability at the hip and 56% at the spine. Logistic regression showed that a BMI < 25.1 kg/m(2) was independently associated with osteoporosis risk (OR = 10.0; 95%CI 1.3-76); no independent effect emerged for FEV1% (

Ischemic colitis in the elderly: predictors of the disease and prognostic factors to negative outcome.

OBJECTIVE: Ischemic colitis (IC) poses a challenge for physicians, especially in elderly patients. The aim of this study was to identify predictors of the disease and to assess the factors predicting its evolution in elderly people. MATERIAL AND METHODS: A retrospective study was undertaken in patients with IC admitted to Padua General Hospital between 2003 and 2008. Only patients with biopsy-proven IC were considered. Fifty control subjects were randomly selected from those seen at our units for acute geriatric disease during the same interval. Patients with IC were classified as having either a positive or negative outcome. RESULTS: A total of 46 patients were considered. The risk factors for IC identified from univariate analysis were analyzed in a multivariate logistic regression model and constipation [adjusted odds ratio (OR) 4.8; 95% confidence interval (CI) 1.1-20.1], vasculopathy (OR 4.9; 95% CI 1.4-16.6), hepatitis C virus (HCV) (OR 9.9; 95% CI 1.1-92.9) and cancer (OR 7.5; 95% CI 2.1-26.9) confirmed their independent significance as risk factors. Hematochezia was predictive of a positive outcome (OR 0.07; 95% CI 0.02-0.40), while cancer (OR 3.2; 95% CI 1.2-11.9), HCV positivity (OR 9.6; 95% CI 1.6-56.5), signs of peritonism (OR 4.7; 95% CI 1.2-18.4), localization in the right colon (OR 5.75; 95% CI 1.5-21.9) and increased levels of lactate dehydrogenase (LDH) and urea were independently predictive of a negative outcome. CONCLUSIONS: Elderly patients with IC are characterized by significant comorbidities. The absence of hematochezia and the presence of a concomitant malignancy, HCV, a marked increase in urea and LDH and disease involving only the right colon are factors that may predict a negative outcome in elderly patients.

The effects of the surgical removal of subcutaneous adipose tissue on energy expenditure and adipocytokine concentrations in obese women.

OBJECTIVE: To analyze the effects of the surgical removal of subcutaneous adipose tissue by ultrasound-assisted megalipoplasty (UAM) on energy expenditure and adipocytokine concentrations in obese women. METHODS: Fifteen premenopausal obese women with BMI 37.5+/-6.3 kg/m(2) (range: 30.7-53.6 kg/m(2)) underwent UAM. Body composition (by DEXA), resting metabolic rate (REE) by indirect calorimetry, insulin resistance (by the HOMA method), leptin, C-reactive protein, interleukin-6, resistin and adiponectin were measured before and 1, 3, 28 and 180 days after the procedure. RESULTS: UAM significantly reduced fat mass at day 3, without further changes in the following days. REE increased at day 3 after UAM, returned to baseline levels at day 28 and significantly declined at day 180. Leptin levels transiently increased after UAM and then declined according to fat mass reduction. C-reactive protein, interleukin-6 and resistin levels acutely increased after UAM and then returned to the baseline levels. Adiponectin levels acutely declined after the procedure and then stabilized to a plasma level slightly lower than at baseline. Insulin resistance deteriorated in the acute post-operative phase and then improved. CONCLUSION: The surgical removal of subcutaneous fat was associated to an acute inflammatory reaction with high REE and insulin-resistance. Later on, the metabolic effects of fat mass removal appeared, with a reduction of leptin levels and REE and an improvement of insulin resistance.

Lower extremity motor performance and body mass index in elderly people: the Italian Longitudinal Study on Aging.

OBJECTIVES: To test the association between body mass index (BMI) and lower extremity motor performance in elderly people. DESIGN: Multicenter, cross-sectional, observational study. SETTING: A sample of individuals aged 65 and older recruited for the baseline survey of the Italian Longitudinal Study on Aging. PARTICIPANTS: Two thousand six hundred seventy-two individuals (1,436 men, 1,236 women) independent with transfers and toileting and independent or requiring assistance for bathing or dressing. MEASUREMENTS: Motor function was assessed using a Motor Performance Test (MPT), with a set of six tasks exploring lower extremity performance (LEP): rising once from a chair, turning in a half circle, tandem walking, standing on one leg, stair climbing, and walking 5 m. RESULTS: The highest prevalence rates of difficulty in performing the tasks occurred in men and women, respectively, in tandem walking (14%, 28%), stair climbing (17.0%, 43%) and walking 5 m (15%, 30%). In both sexes, moderate (men: odds ratio (OR)=1.99, 95% confidence interval (CI)=1.16-3.43; women OR=2.07, 95% CI=1.18-3.65) and severe obesity (men: OR=3.45, 95% CI=1.21-9.89; women: OR=3.16, 95% CI=1.43-6.95) were each independently associated with overall motor performance impairment after adjusting for age, smoking, and comorbidity. Best performance was generally observed in the normal-weight and overweight groups. CONCLUSION: The results confirm that, in both sexes, overweight is not related to motor impairment. Only in women, low BMI is associated with higher probability of overall motor performance impairment. These data suggest that moderate obesity should be distinguished from severe obesity when assessing the relationship between BMI and LEP.

An adequate threshold for body mass index to detect underweight condition in elderly persons: the Italian Longitudinal Study on Aging (ILSA).

BACKGROUND: The present study aims at defining a body mass index (BMI) threshold for risk of being underweight in elderly persons on the basis of the BMI distribution in a large Italian population-based sample and on its ability to predict short-term mortality. METHODS: At baseline (1992), BMI was obtained for 3110 (1663 males and 1447 females) persons aged 65-84 participating in the Italian Longitudinal Study on Aging (ILSA). BMI and risk factors (age, sex, education, smoking status, disability, and disease status) have been considered for their potential association with 4-year all-cause mortality. Information on vital status at 1995 was obtained for 2551 participants. RESULTS: The fifth centile of BMI was well approximated by a value of 20 for both sexes. Also in both sexes, at a BMI value of 24 the a posteriori probability of death started to increase, doubling at a value of 22 for men and 20 for women. Crude mortality was 14.6% for men and 9.8% for women. The hazard ratios and confidence intervals (CIs) comparing mortality for each BMI two-unit class to the 26-28 class, after adjusting for confounding variables, showed significantly higher rates only for BMI values below 20 (2.9; 95% CI, 1.2-7.0), although a consistent increase in hazard ratio (1.6; 95% CI, 0.9-3.0) already appeared for the 20-22 BMI group. CONCLUSIONS: Our study confirms that low BMI is an independent predictive factor of short-term mortality in elderly persons. A BMI value of 20 kg/m2 seems to be a reliable threshold for defining underweight elderly persons at high risk. Nevertheless, more careful clinical and nutritional management should also be applied to elderly persons with higher BMI values.

Total and regional body composition and energy expenditure in multiple symmetric lipomatosis.

AIMS: The aim of the present study was to investigate possible alterations in body composition and resting energy expenditure (REE) in type 1 multiple symmetric lipomatosis (MSL). SUBJECTS AND METHODS: Thirteen men aged from 40 to 78 years affected by type I MSL were compared with 13 healthy control subjects. Fat mass (FM) and fat-free mass (FFM) were determined by DEXA using both standard analysis and specifically for the lipomatous region. REE was measured by indirect calorimetry. RESULTS: FM was higher in MSL subjects at proximal arm level, but significantly lower at distal leg level than in controls (left 1.63+/-0.55 vs. 2.26+/-0.49 kg, P<0.05; right 1.63+/-0.53 vs. 2.40+/-0.54 kg, P<0.01). Arm FFM was similar in the two groups, while distal leg FFM was significantly lower in MSL cases (left: 7.8+/-1.3 vs. 8.7+/-0.8 kg, P<0.05; right: 8.0+/-1.5 vs. 9.2+/-0.9 kg, P<0.05). FFM strongly correlated with REE (r:0.86;P<0.001). REE, expressed as an absolute value and adjusted for FFM (1830+/-215 vs. 1675+/-120 kcal, P<0.05) was higher in MSL patients. CONCLUSION: In conclusion, MSL patients had a marked FFM and FM atrophy in the lower segments of the legs and an altered energy expenditure (hypermetabolism).

Multiple symmetric lipomatosis may be the consequence of defective noradrenergic modulation of proliferation and differentiation of brown fat cells.

Multiple symmetric lipomatosis (MSL) is an inherited disorder in which enlarging and unencapsulated lipomas symmetrically develop in the subcutaneous tissue of the neck, shoulders, mammary, and truncal regions. In some cases, it is associated with mitochondrial DNA abnormalities. The pathogenesis of MSL is completely unknown, although the fat deposits may be due to a neoplastic-like proliferation of functionally defective brown adipocytes. It has recently been demonstrated that the beta(3)-adrenergic receptor is the functionally relevant adrenergic receptor subtype in brown adipocytes and that its stimulation by noradrenaline (NA) modulates the expression of genes, such as uncoupling protein (UCP)-1 and inducible nitric oxide synthase (iNOS), involved in fat cell proliferation and differentiation. Furthermore, Trp64Arg mutation of the beta(3)-adrenoceptor has been implicated in lower NA activity in adipose tissues. The aim of this study was to investigate the molecular and functional characteristics of MSL adipocytes and to analyse the effects of nitric oxide (NO) on the proliferation/differentiation of MSL adipocytes in culture, and the relevance of putative noradrenergic deficit in the development of lipomas in MSL patients. Cultured MSL adipocytes were able to synthesize UCP-1 (the selective marker of brown adipocytes), but unlike that of normally functioning brown fat cells, the expression of the UCP-1 gene was not significantly induced by NA. NA is also defective in inducing iNOS gene expression, thus leading to reduced NO production and a consequent reduction in the anti-proliferative, adipogenic (mitochondrial biogenesis) effects of NA on MSL cells. Furthermore, the transcriptional peroxisome proliferator-activated receptor gamma co-activator-1 (PGC-1), which plays a key role in the sympathetic-stimulated mitochondrial biogenesis of brown adipocytes, is expressed but not induced by NA in MSL cells, as it is in brown adipocytes. The study did not find any association between beta(3)-adrenoceptor gene polymorphism and noradrenergic signalling defects in MSL subjects with or without mitochondrial DNA mutations.