Sex steroids regulate liver fat content and body fat distribution in both men and women: a study in transgender persons

Context Liver fat content and visceral fat volume are associated with insulin resistance and cardiovascular disease and are higher in men than in women. Objective To determine the effect of estradiol and testosterone treatment on liver fat and visceral fat in transgender persons. Design Open-label intervention study (SHAMVA) with a 1-year follow-up. Setting Gender clinic in a hospital. Patients 8 trans women and 18 trans men receiving hormone treatment. Interventions Trans women received an antiandrogen and after 6 weeks estradiol was added. Trans men were randomized to receive triptorelin, testosterone, and anastrozole for 12 weeks or triptorelin and testosterone for 12 weeks, followed by only testosterone until week 52. Main outcome measures Liver fat content, visceral and abdominal subcutaneous fat volume, measured by magnetic resonance spectrometry or imaging at baseline, 6, 8, 18, and 58 weeks in transwomen or at baseline; at 6 and 12 weeks in trans men with anastrozole; and at 52 weeks in trans men without anastrozole. Results In trans women, liver fat content decreased by 1.55% (-2.99 to -0.12) after 58 weeks, compared to week 6. Visceral fat did not change. In trans men with anastrozole, the liver fat content and visceral fat volume did not change. In trans men without anastrozole, after 52 weeks, liver fat content increased by 0.83% (0.14 to 1.52) and visceral fat volume increased by 34% (16 to 51). Conclusions Sex hormones regulate liver fat content and visceral fat in men and women.Clinical epidemiolog

Mechanisms underlying electro-mechanical dysfunction in the Zucker diabetic fatty rat heart: a model of obesity and type 2 diabetes

Diabetes mellitus (DM) is a major and worsening global health problem, currently affecting over 450 million people and reducing their quality of life. Type 2 diabetes mellitus (T2DM) accounts for more than 90% of DM and the global epidemic of obesity, which largely explains the dramatic increase in the incidence and prevalence of T2DM in the past 20 years. Obesity is a major risk factor for DM which is a major cause of morbidity and mortality in diabetic patients. The electro-mechanical function of the heart is frequently compromised in diabetic patients. The aim of this review is to discuss the pathophysiology of electro-mechanical dysfunction in the diabetic heart and in particular, the Zucker diabetic fatty (ZDF) rat heart, a well-studied model of T2DM and obesity

Neural control of hepatic lipid metabolism: A (patho)physiological perspective

Our body is well designed to store energy in times of nutrient excess and release energy in times of need. This adaptation to the external environment is achieved by both humoral factors and the autonomic nervous system. Already in the 19th century, Claude Bernard pointed out the importance of the autonomic nervous system in the control of glucose metabolism. In the next century, the discovery of insulin and the development of techniques to measure hormone concentrations shifted the focus of the control of metabolism to the secretion of hormones, thus functionally "decapitating" the body. Just before the end of the 20th century, starting with the discovery of leptin in 1994, the control of energy metabolism went back to our heads. Today, the autonomic nervous system is acknowledged as one of the important determinants of liver metabolism and as a possible treatment target. This thesis investigates the role of the autonomic nervous system in the control of hepatic lipid metabolism during different physiological conditions. We found that the sympathetic and parasympathetic nervous system represent complimentary forces, fine-tuning hepatic lipid metabolism during different nutritional states

Hypothalamic control of hepatic lipid metabolism via the autonomic nervous system

Our body is well designed to store energy in times of nutrient excess, and release energy in times of food deprivation. This adaptation to the external environment is achieved by humoral factors and the autonomic nervous system. Claude Bernard, in the 19th century, showed the importance of the autonomic nervous system in the control of glucose metabolism. In the 20th century, the discovery of insulin and the development of techniques to measure hormone concentrations shifted the focus from the neural control of metabolism to the secretion of hormones, thus functionally "decapitating" the body. Just before the end of the 20th century, starting with the discovery of leptin in 1994, the control of energy metabolism went back to our heads. Since the start of 21st century, numerous studies have reported the involvement of hypothalamic pathways in the control of hepatic insulin sensitivity and glucose production. The autonomic nervous system is, therefore, acknowledged to be one of the important determinants of liver metabolism and a possible treatment target. In this chapter, we review research to date on the hypothalamic control of hepatic lipid metabolism

The use of D-dimer in specific clinical conditions: a narrative review

The use of D-dimer in combination with a clinical decision rule has been widely investigated in pulmonary embolism and deep venous thrombosis. Although it has been shown to be safe in excluding venous thromboembolism, the clinician is often faced with specific situations in which the use of D-dimer is controversial. We review the best available evidence on these patients. We conclude that it is not safe to use D-dimer testing in patients with symptoms of a venous thromboembolism for over 14 days, patients receiving therapeutic heparin treatment and patients with suspected deep venous thrombosis during oral anticoagulant therapy. In these populations the levels of D-dimer can be lower then expected giving rise to false-negative results. It is safe to use D-dimer testing in combination with a clinical decision rule in patients of all ages, patients presenting with a suspected recurrent venous thromboembolism or inpatients with suspected pulmonary embolism. As patients with recurrent venous thromboembolism, elderly patients and inpatients have higher levels of D-dimer, D-dimer testing has a low specificity and the need for additional radiological testing is increase

Hepatic denervation and dyslipidemia in obese Zucker (fa/fa) rats

Human and animal studies increasingly point toward a neural pathogenesis of the metabolic syndrome, involving hypothalamic and autonomic nervous system dysfunction. We hypothesized that increased very-low-density lipoprotein-triglyceride (VLDL-TG) secretion by the liver in a rat model for dyslipidemia, that is, the obese Zucker (fa/fa) rat, is due to relative hyperactivity of sympathetic, and/or hypoactivity of parasympathetic hepatic innervation. To test the involvement of the autonomic nervous system, we surgically denervated the sympathetic or parasympathetic hepatic nerve in obese Zucker rats. Our results show that cutting the sympathetic hepatic nerve lowers VLDL-TG secretion in obese rats, finally resulting in lower plasma TG concentrations after 6 weeks. In contrast, a parasympathetic denervation results in increased plasma total cholesterol concentrations. The effect of a sympathetic or parasympathetic denervation of the liver was independent of changes in humoral factors or changes in body weight or food intake. In conclusion, a sympathetic denervation improves the lipid profile in obese Zucker rats, whereas a parasympathetic denervation increases total cholesterol levels. We believe this is a novel treatment target, which should be further investigated

Hypothalamic control of energy metabolism via the autonomic nervous system

The hypothalamic control of hepatic glucose production is an evident aspect of energy homeostasis. In addition to the control of glucose metabolism by the circadian timing system, the hypothalamus also serves as a key relay center for (humoral) feedback information from the periphery, with the important role for hypothalamic leptin receptors as a striking example. The hypothalamic biological clock uses its projections to the preautonomic hypothalamic neurons to control the daily rhythms in plasma glucose concentration, glucose uptake, and insulin sensitivity. Euglycemic, hyperinsulinemic clamp experiments combined with either sympathetic-, parasympathetic-, or sham-denervations of the autonomic input to the liver have further delineated the hypothalamic pathways that mediate the control of the circadian timing system over glucose metabolism. In addition, these experiments clearly showed both that next to the biological clock peripheral hormones may "use" the preautonomic neurons in the hypothalamus to affect hepatic glucose metabolism, and that similar pathways may be involved in the control of lipid metabolism in liver and white adipose tissu

Early induction of hepatic deiodinase type 1 inhibits hepatosteatosis during NAFLD progression

10.1016/j.molmet.2021.101266Molecular Metabolism53101266