Isolated hypercholesterolemia leads to steatosis in the liver without affecting the pancreas

Abstract Background Lipid accumulation in the liver and pancreas is primarily caused by combined hyperlipidemia. However, the effect of isolated hypercholesterolemia without hypertriglyceridemia is not fully described. Therefore, our aim was to investigate whether hypercholesterolemia alone leads to alterations both in hepatic and pancreatic lipid panel and histology in rats. Methods Male Wistar rats were fed with 2% cholesterol +0.25% cholate-supplemented diet or standard chow for 12 weeks. Blood was collected at weeks 0, 4, 8 and 12 to measure serum cholesterol and triglyceride levels. At week 12, both the pancreas and the liver were isolated for further histological and biochemical analysis. Hepatic and plasma fatty acid composition was assessed by gas chromatography. Expression of mRNA of major enzymes involved in saturated/unsaturated fatty acid synthesis was analyzed by qPCR. In separate experiments serum enzyme activities and insulin levels were measured at week 9. Results At week 12, rats fed with 2% cholesterol +0.25% cholate-supplemented diet were characterized by elevated serum cholesterol (4.09 ± 0.20 vs. 2.89 ± 0.22 mmol/L, *p < 0.05) while triglyceride (2.27 ± 0.05 vs. 2.03 ± 0.03 mmol/L) and glucose levels (5.32 ± 0.14 vs. 5.23 ± 0.10 mmol/L) remained unchanged. Isolated hypercholesterolemia increased hepatic lipid accumulation, hepatic cholesterol (5.86 ± 0.22 vs. 1.60 ± 0.15 ng/g tissue, *p < 0.05) and triglyceride contents (19.28 ± 1.42 vs. 6.78 ± 0.71 ng/g tissue, *p < 0.05), and hepatic nitrotyrosine level (4.07 ± 0.52 vs. 2.59 ± 0.31 ng/mg protein, *p < 0.05). The histology and tissue lipid content of the pancreas was not affected. Serum total protein level, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities remained unchanged in response to isolated hypercholesterolemia while serum alkaline phosphatase activity (ALP) significantly increased. Plasma insulin levels did not change in response to isolated hypercholesterolemia suggesting an intact endocrine function of the pancreas. Isolated hypercholesterolemia caused a significantly increased hepatic and serum fatty acid level associated with a marked alteration of fatty acid composition. Hepatic expression of Δ9-desaturase (SCD1) was increased 4.92×, while expression of Δ5-desaturase and Δ6-desaturase were decreased (0.447× and 0.577×, respectively) due to isolated hypercholesterolemia. Conclusions Isolated hypercholesterolemia leads to hepatic steatosis and marked alterations in the hepatic lipid profile without affecting the pancreas. Altered fatty acid profile might mediate harmful effects of cholesterol in the liver

Evolution and development of the Indian monsoon

© Springer Nature Switzerland AG 2020. The Indian monsoon is a complex oceanic-atmospheric-coupled mechanism of the tropics that plays a key role in inter-hemispheric heat transfer on Earth. The summer monsoon brings moisture to the highly populated South Asian countries and affects the livelihood of more than a billion people. The intensity of the monsoon significantly influences the ecological diversity and hydrological reservoirs across the South Asian region. However, the intensity of the monsoon greatly varies spatially and temporally, driven by both external and internal forcing factors. Modeling and palaeoclimatic studies indicate several phases of strong and weak summer monsoon rainfall caused by changes in solar insolation, snow accumulation in western Europe, El Niño-Southern Oscillation, North Atlantic Oscillations and sea surface temperature in the Indian and Pacific Oceans. The initiation and strengthening of the Indian monsoon during the middle-late Miocene are sometimes linked with phases of major surface uplift of the Himalayan and/or Tibetan Plateau. The Plio-Pleistocene glaciation prompted a strong winter monsoon and a weak summer monsoon. During the early Holocene, the summer monsoon strengthened and subsequently weakened with two major phases of sudden rainfall reduction at ~8.2 and ~4.2 kyr BP; the latter event caused significant societal impact including the migration of population of the Indus Valley Civilization. In the last millennium, the Indian summer monsoon (ISM) was strong during the Medieval Warm Period (MWP) now designated as Medieval Climate Anomaly (MCA) and Current Warm Period (CWP), punctuated by a weak phase during the Little Ice Age (LIA). Meteorological records indicate an increasing trend in the intensity and frequency of extreme rainfall events in the last few decades leading to widespread floods and droughts. High-resolution climatic records from marine as well as continental archives improve our understanding of Indian monsoon variability and its forcing factors on different time scales