There exists a close synchrony between the endocrine system, adipose tissue, and lipid metabolism. The novel concept of lipocrinology describes “the study of the inter-relationship between lipid metabolism and endocrine function in health and disease”. Dyslipidemia is commonly seen in endocrine disorders and lipid abnormalities may point to underlying endocrine illness in general clinical practice. Since the prevalence of both lipid disorders and endocrine diseases is on the rise, it is prudent to understand the multifaceted relationship between lipid health and endocrine health. This chapter introduces the concept of lipocrinology, highlighting the myriad ways in which this inter-relationship between hormones and lipids is clinically relevant and important.
The concept of “lipocrinology” was proposed by us to describe “the study of the inter-relationship between lipid metabolism and endocrine function in health and disease”.1 There exists a close synchrony between the endocrine system and lipid and lipoprotein metabolism, and this is reflected in both normal physiology and pathophysiological states.
Dyslipidemia is a common occurrence in clinical practice and accounts for greater than half the global burden of cardiovascular disease and has been attributed to cause over 4 million deaths per annum as per World Health Organization (WHO) 2002 report.2 The prevalence of hypercholesterolemia was estimated to range from 3 to 53% in men and 4 to 40% in women in the WHO MONICA project that collected data from across 32 populations in 19 countries.4 As per the Indian Council of Medical Research-India Diabetes Study (ICMR-INDIAB), there was a disturbingly high prevalence of dyslipidemia in individuals more than or equal to 20 years age in both rural and urban regions, with hypercholesterolemia in 13.9%, hypertriglyceridemia in 29.5%, reduced high-density lipoprotein cholesterol (HDL-C) in 72.3%, and increased low-density lipoprotein cholesterol (LDL-C) in 11.8%. As high as 79% individuals had abnormalities in at least one of the lipid parameters studied.3
Understandably, a significant amount of medical research and literature has been dedicated to the management of dyslipidemia and atherosclerosis and the reduction of cardiovascular risk. Statins have revolutionized the management of lipid disorders and several other classes of lipid-lowering drugs including fibrates, ezetimibe, bile acid sequestrants, and peroxisome proliferator-activated receptor alpha (PPARα) agonists have been added to the armamentarium. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are another novel class of lipid-lowering drugs which hold great promise for the future. Many of these drugs, including the currently available lipid-lowering drugs, have pleiotropic effects that include endocrine effects as well.
However, despite clear evidence that dyslipidemia is a major driver for comorbidity and mortality related to noncommunicable diseases, it remains an underdiagnosed and undertreated anomaly in both developed and developing countries. The awareness regarding hypercholesterolemia was seen in only 0–33% men and women in the WHO MONICA project. Moreover, only 50% of individuals who were receiving lipid-lowering drugs had attained target cholesterol levels.4 Similar alarming data was gathered between 1998 and 2007 from eight high- and middle-income countries. The percentage of individuals with undiagnosed high cholesterol varied from 16% in United States to 78% in Thailand. Of those who were being treated, the percentage of individuals achieving target levels ranged from 4% in Germany to 58% in Mexico.5 Several factors contribute to this—clinical inertia in diagnosis and management of dyslipidemia, suboptimal dosing, drug intolerance, and poor drug adherence. At the same time, inability to diagnose and address other conditions such as endocrine disorders that contribute to abnormal lipoprotein homeostasis may result in suboptimal control.
In recent times, the prevalence of both dyslipidemia and endocrine disorders is increasing due to genetic as well as environmental factors. This is likely to create greater challenges in the clinical management of lipid disorders as well as endocrinopathies. But at the same time, this is also expected to create new opportunities in furthering our understanding of the interface between endocrinology and metabolism and development of new therapeutic possibilities. Several newer drugs that have effects on lipid and glucose metabolism as well hormonal milieu are in development.
In such a scenario, there is a clear need to improve our understanding of endocrine system and lipid metabolism and how these work in tandem in the causation of noncommunicable diseases. Hence, the novel field of lipocrinology is not only relevant, but also the need of the hour.
LIPID METABOLISM: EFFECTS ON ENDOCRINE PHYSIOLOGY
Lipids play an essential role in the development and functioning of key endocrine organs. Lipids are the precursor molecules in the enzyme pathways leading to steroid hormone synthesis in several endocrine tissues, including adrenals and gonads. Intracellular lipid metabolites such as inositol triphosphate and diacylglycerol are essential second messengers involved in the cellular signaling pathways for a wide variety of hormones. Lipids are an important energy fuel for several energy-intensive processes including spermatogenesis and oogenesis. Additionally, several lipid-lowering drugs have been demonstrated to have endocrine effects other than lowering of lipid levels.
THE ADIPOSE TISSUE AS AN ENDOCRINE ORGAN
Adipose tissue, in its own merit, is now considered as a key endocrine organ that works in tandem with other endocrine organs such as the adrenals, gonads, pancreas, thyroid, and pituitary to regulate energy homeostasis, glucose and lipid metabolism, inflammation and endothelial functions. Adipose tissue dysfunction and lipotoxicity are increasingly recognized as a significant contributor to diabetes pathophysiology, including impairment of insulin secretion and insulin action. Lipotoxicity also forms the common link between diabetes and comorbid conditions such as cardiovascular disease and nonalcoholic fatty liver disease. Furthermore, genetic or acquired lipodystrophies are themselves associated with disturbances in endocrine functions.
THE ENDOCRINE EFFECTS ON LIPID METABOLISM
On the other end of the spectrum, all players of the endocrine system modulate the distribution and the differentiation of adipose tissue and regulate its functions. Diseases of the endocrine system, be they hormone deficiency states or hormone excess states, are associated with significant alterations in lipid metabolism that may manifest clinically as dyslipidemia. Indeed, detection of dyslipidemia in general practice merits detailed clinical assessment to exclude endocrinopathies as a secondary cause of dyslipidemia. Dyslipidemia is also the main contributing factor causing increased cardiovascular risk seen in several endocrine disorders and while it may be amenable to correction by adequate treatment of the underlying endocrinopathy, it may need to be addressed separately. Likewise, several drugs used in the management of endocrine diseases can have clinically meaningful effects on lipid parameters and adipose tissue health.
LIPOCRINOLOGY: A STEP TOWARD NEWER INSIGHTS
The subject of lipocrinology covers these varied aspects of the complex and multifaceted interplay between the endocrine system, adipose tissue, and lipid metabolism. The framework, as outlined in box 1 provides an improved understanding of the physiological links between hormones and metabolism, particularly lipid metabolism and the pathophysiological changes in various endocrine disease states. An understanding of these inter-relationships can improve clinical decision-making and management by improving vigilance for lipid disorders in the practice of endocrinology and endocrine disorders in the practice of lipidology. The concept is relevant to not just practicing endocrinologists, but also general physicians, internists, and cardiologists. This novel discipline has the potential to further research in both lipidology and endocrinology.
This book is dedicated to these aspects of lipocrinology. In the first section “Lipocrinology in Endocrinology”, the contribution of various endocrine organs to lipid health and the pathogenesis of dyslipidemia in endocrine disease are discussed.
The clinical utility of lipid parameters in diagnosis of endocrinopathies and their impact on the clinical course and prognosis of endocrinopathies is also considered. We also discuss the need for lipid vigilance in endocrine diseases. The second section “Endocrinology in Lipocrinology” is dedicated to the role of the adipose tissue as an endocrine organ, the role of lipotoxicity in diabetes, and the Asian lipophenotype, endocrine aspects of lipodystrophies, and endocrine vigilance in lipid disorders. The final section focuses on “Management Issues in Lipocrinology” and elaborates upon the effects of lipid-lowering drugs in management of endocrinopathies, lipotropic effects of drugs used in endocrinology and diabetes, and endocrine effects of lipid-lowering drugs including PCSK9 inhibitors.
We hope this book sensitizes the readers to a greater understanding of lipocrinology and inspires further research.
- Kalra S, Priya G. Lipocrinology – the relationship between lipids and endocrine function. Drugs Context. 2018;7:212514.
- World Health Organization. Quantifying selected major risks to health. The World Health Report 2002. Reducing Risks, Promoting Healthy Life. Geneva: World Health Organization; 2002:47–97.
- Joshi SR, Anjana RM, Deepa M, et al. ICMR-INDIAB Collaborative Study Group. Prevalence of dyslipidemia in urban and rural India: the ICMR-INDIAB study. PLoS One. 2014;9(5):e96808.
- Tolonen H, Keil U, Ferrario M, et al. WHO MONICA Project. Prevalence, awareness and treatment of hypercholesterolaemia in 32 populations: results from the WHO MONICA Project. Int J Epidemiol. 2005;34(1):181–92.
- Roth GA, Fihn SD, Mokdad AH, et al. High total serum cholesterol, medication coverage and therapeutic control: an analysis of national health examination survey data from eight countries. Bull World Health Organ. 2011;89(2):92–101.